Making Cholesterol-Lowering Statin Drugs More Effective Against Cancer - Cancer Treatments - From Research To Application

25/2/22, 18:33 Making Cholesterol-Lowering Statin Drugs More Effective Against Cancer - Cancer Treatments - from Research to Application
Cancer Treatments – from Research to Application

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POSTED ON JULY 21, 2019 BY DANIEL

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Statins and Cancer
Welcome
Dear Friends, I am currently on holiday, travelling and with little access to the computer, but recently I
came across interesting information related to the use of Statins to fight cancer, and would like to share Marorsan
that with you as soon as possible. So I decided to allocate a day and consolidate this important
My Profile
information on Statins. It may not be very well written post but I hope it helps you. Logout
This important information is related to the following:
a Statin that seems to be the most effective against cancer of all Statins Recommended
a specific diet that should go with it, and Supplements
a case report of a ovarian cancer patient (a doctor) using this combo and obtaining complete
remission
First, here is a little background for those new to the subject:
Statins (e.g. atorvastatin, lovastatin, simvastatin, pravastatin, pitavastatin, rosuvastatin, mevastatin,

cerivastatin and fluvastatin) are a group of (FDA approved) drugs used to lower cholesterol, reducing
illness and mortality in those who are at high risk of cardiovascular disease.
However, during the past years Statins have been found to also have important anticancer action,
possibly related to their capability of inhibiting/reducing cholesterol production. There is a large amount
of science on that (Ref.), some of which will be discussed below, as well as meta-analysis trying to
validate the findings from the laboratory.
In line with all the scientific discoveries from the academic field, mevalonate pathway and cholesterol
production related to that are key in cancer (Ref.), and as a results their modulation can help fight Recent Comments
cancer. Statins are inhibiting an enzyme (HMGCR) which is essential for the synthesis of mevalonate (a
https://www.cancertreatmentsresearch.com/cholesterol-lowering-statin-drugs-to-fight-cancer/ 1/27
precursor for the biosynthesis of  johan on Colon and Colorectal

cholesterol). This leads to a lower Cancer
cholesterol production in cells. Cholesterol  Jcancom on Colon and Colorectal

Cancer
starvation in hepatocytes increases
expression of LDLR, in turn facilitating  johan on Colon and Colorectal
Cancer
uptake of LDL particles from blood, which
reduces blood cholesterol (Ref.). However,  johan on Colon and Colorectal
Cancer
note that because Statins inhibit the
mevalonate pathway, they do not only  johan on Colon and Colorectal
Cancer
prevent the synthesis of cholesterol, but
also inhibit Ras/MEK/ERK and Ras/mTOR  Tomaz26 on Colon and Colorectal
Cancer
pathways, in connection to geranylgeranyl
pyrophosphate (GGPP) depletion (Ref.1,  Shanti on Unlocking Zinc’s
Potential to Fight Cancer
Ref.2, Ref.3). GGPP is an intermediate on
the mevalonate pathway, essential for the anchoring of Ras protein to the cell membranes (Ref.). (Here  Inabari on Unlocking Zinc’s
is a map showing where HMGCR and GGPP are located on the mevalonate pathway.).
 Shanti on Unlocking Zinc’s
Geranylgeranyl pyrophosphate (GGPP) depletion could be an important mechanism leading to
anticancer effects since it has been demonstrated that supplementation with Geranylgeraniol (a  cl812271 on Unlocking Zinc’s
substance found in various foods) can inhibit the anticancer effects of statins (see discussion below).
Indeed, inside the cells there is a salvage pathway that converts Geranylgeraniol into Geranylgeranyl  gummybears on pH in Cancer &
Tumor Acidification: A Top Treatment
pyrophosphate (GGPP) (Ref.1, Ref.2).
Strategy
 jsanz421 on 3 Bromopyruvate
In some of my previous posts I already discussed various ways to modulate mevalonate pathway and as
a result cholesterol (and Geranylgeranyl pyrophosphate) (Ref.), and latter I even consolidate all those  jsanz421 on 3 Bromopyruvate
approaches in an “Anti Cholesterol Strategy” (Ref.). Yet, I never discussed Statins in more details. Now,  Daniel on Some thoughts on 3BP
given this recent information indicating ways to increase the effectiveness of Statins as well as a  Daniel on Unlocking Zinc’s
successful case report after using that approach, I think it’s time to have a dedicated post to Statins. Of- Potential to Fight Cancer
course, there is so much to write about Statins and cancer, but here I will try to stick to the aspects that  Daniel on pH in Cancer & Tumor
are most important for their application against cancer. Acidification: A Top Treatment
Strategy
Laboratory research indicates that Statins may be relevant in the fight against various types of cancer  gummybears on pH in Cancer &
Tumor Acidification: A Top Treatment
Strategy
Statins can represent useful tools to fight cancer either alone or in combination with conventional
therapies including radio- and chemo-therapy, in various cancer types including:  purplegolfchic on Unlocking
Zinc’s Potential to Fight Cancer
gastric cancer (Ref.)  Pulse on Colon and Colorectal

Cancer
ovarian cancer (Ref.)
head and neck cancer (Ref.)  Daniel on Colon and Colorectal
Cancer
endometrial cancer (Ref.)
breast cancer (Ref.1, Ref.2)
glioblastoma (Ref.)
prostate cancer (Ref1, Ref.2.) Recommended
paragangliomas (Ref.) Book
blood cancers (leukemia and lymphoma) (Ref.)
colon cancer (Ref.1, Ref.2)
pancreatic cancer (Ref.)
hepatocellular carcinoma (Ref.)
etc.
The above are just a few examples of references, but the reader will be able to find much more
references for most type of cancers, as this is a subject intensively investigated in the academic space.
So far, in real life, positive results were observed, but more moderate compared to the laboratory
Indeed, going from laboratory to real life studies, the results are sometimes mixed. Such studies are
either looking at correlating the use of Statins with cancer incidence or cancer recurrence and mortality.
For example, a Meta-Analysis on the association of Statins and cancer incidence did not showed a
statistically significant difference induced by the use of statins (Ref.). Also, studies such as combining
Statins with sorafenib in advanced hepatocellular carcinoma did not show signs of improved survival
(Ref.). Forum: Recent Posts
Other studies on the other hand, indicated positive associations between the long-term Statins use and
RE: IVC and (or?) Ferroptosis
an improved overall survival in breast cancer patients (Ref.). Positive association between the use of when Immunotherapy only
Statins and the improved outcomes have also been identified in colorectal cancer (Ref.), renal cell but I'm really not the person to
carcinoma (Ref.), pancreatic cancer (Ref.), esophageal cancer (Ref.), prostate cancer (Ref.), ovarian answer questions on th...
By johan, 3 mins ago
cancer (Ref.) and breast cancer (Ref.). Nielsen et al. showed an association of Statins use and a
reduced cancer-related mortality for 13 malignancies, e.g. pancreatic cancer and cervical cancer (Ref.). RE: IVC and (or?) Ferroptosis
when Immunotherapy only
Overall, most studies indicate a positive impact of the use of Statins on the survival of patients with Glut1 is used for vitamin c
recycling so in theory ther...
various cancer types. In full resonance with these studies, Care Oncology Clinic recently reported By johan, 12 mins ago
positive results from patients using a cocktail of four re-purposed drugs including one Statin drug
(Ref.). This cocktail succeeded to help double the average survival time in Glioblastoma patients.
@j for example, IVC is the pro-
Therefore as we can see from these results, while the research in the lab indicates that Statins can be oxidant strategy and ora...
effective tolls to fight and kill cancer cells, in reality the results are there but more moderate. While By AbidingToday, 18 mins ago
having even moderate results is highly valuable in advanced cancers, the question is how we can RE: IVC and (or?) Ferroptosis
maximise the effectiveness of Satins so that we obtain not only slow down of tumour growth, but when Immunotherapy only
tumour death? @j yes, I agree on the life and
health extension benefi...
By AbidingToday, 21 mins ago
How to Make Statins Work Better Against Cancer? RE: IVC and (or?) Ferroptosis
It is indeed known that Statins is a group of drugs containing various drugs that have different @abidingtoday many already
absorption in the body and different life time in patient’s blood. In addition, as discussed below, there use vitamin c in such a stra...
are other aspects that have to be considered in order to get the best out of Statins value. Here are some
approaches that are expected to increase the effectiveness of Statins against cancer: RE: IVC and (or?) Ferroptosis
1. Reduce cancer cells resistance to Statins with the help of the FDA approved drug Dipyridamole
@j honestly, I still like the
metronomic oral C strateg...
Statins inhibit the rate-limiting enzyme of the mevalonate (MVA) pathway called HMG-CoA By AbidingToday, 48 mins ago
reductase (HMGCR). This is also the mechanism through which it is believed that statins kill cancer.
However, it seems that most cells have a way to overcome the HMGCR inhibition with the help of the
sterol regulatory element-binding protein 2 (SREBP2). Using Dipyridamole, a FDA approved drug,
I have never looked at
will block SREBP2 activation and thus, maintain the effectiveness of Statins (Ref.1, Ref.2).
combining vitamin c with citric
. ...
2. Use lipophilic Statins for better intracellular access
It has been suggested that lipophilic statins (e.g. atorvastatin, simvastatin, lovastatin) are more RE: IVC and (or?) Ferroptosis
effective than hydrophilic statins (e.g. pravastatin and rosuvastatin) in cancer treatment. This may when Immunotherapy only
be due to the fact that lipophilic statins are able to cross the biological membranes and they have @j citric acid would probably
be taken in higher doses...
greater intracellular access (Ref.). Here is a paper classifying lipophilic or hydrophilic statins, in the By AbidingToday, 1 hour ago
“Additional file 3” (Ref.).
RE: What to take/stop during

.
Chemo days?
3. Use Statins that have longer lifetime and high anti-cancer effectivness
@corsaro1 I forgot to add your

In laboratory studies, it has been found that continual inhibition of HMGCR is necessary to induce username in the above po...
apoptosis. However, many statins have a short half-life s due to their uptake into the liver and By johan, 1 hour ago
subsequent metabolism by cytochrome P450. What is required on the other hand is a statin that RE: IVC and (or?) Ferroptosis
would be constantly present in the blood. Therefore, one statin to have half-life about 12h and that when Immunotherapy only
would be taken 2x/day every 12h would be perfect. Although I would guess that Atorvastatin would yesterday Tomaz26 made some
interesting observations in...
fit this requirement, according to this publication (Ref.), Pitavastatin is the only statin that fits all
By johan, 1 hour ago
requirements for anti-cancer treatment.
Indeed, this older study indicates that Pitavastatin has a better pharmacokinetic profile
compared to Atorvastatin (Ref.), with the best bio availability (Ref.).
Also, studies on pancreatic cells showed that Pitavastatin is one of the most effective anti-
proliferative statins (Ref.)
More Recent
.
Posts
So based on it’s anticancer action and based on the relatively long half-time (~12h) (Ref.) the
More Recent Comments
statin of choice is Pitavastatin. If Pitavastatin is not available, the next statin I would chose is
Atorvastatin given it’s very long half-time (~14 hours). If non of this two are available, the next
statin would chose is Simvastatin. It is a highly lipophilic one and it is expected to have good
anti-cancer action better than Atorvastatin (at least in pancreatic cancer – Ref.), but the
Statistics since
challenge with it is that its half-time is short (~5h) (Ref.) – so in order to keep a constant level in August 2015
the blood across 24 hours, a patient would have to take it every 5 hours, which is less
Today's Visits:
practical. Here is a paper half life of available statins, in the “Additional file 3” (Ref.).
.
1,711
However, please note that for brain cancer, or brain metastasis, blood brain barrier (BBB) Today's Visitors:
penetration has to also be considered. According to this study (Ref.), “Simvastatin clearly 634
demonstrated a high potential to access to the brain, followed by fluvastatin and cerivastatin, Total Visits:
while atorvastatin, mevastatin, rosuvastatin, and pravastatin scarcely penetrated by passive 7,709,286
diffusion.” Out of these, Simvastatin is best as it has also the longest half-life (about 5h) Total Visitors:
compared to fluvastatin and cerivastatin.
2,196,189
. Total Comments:
10,591
4. Use low geranylgeraniol diet while on Statin
It has been recently found that dietary geranylgeraniol, a fat found in many foods, can limit the
activity of pitavastatin as a potential treatment for cancer. This finding was published in a Nature
Scientific Reports journal (Ref.). Indeed, nearly 20 years ago it has also been shown that Help this work to
Geranylgeraniol inhibits the anti cancer effects of statins (Ref.). Therefore, during the use of continue, please
statins, patients should avoid the use of foods containing high levels of geranylgeraniol, including
rice, sunflower and linseed/flaxseed oil. Actually, it has been already suggested 10 years ago, that Donate
addition of geranylgeraniol can prevent cytotoxic effects of statins and with that also limiting the
toxicities of statins (Ref.), and more recently geranylgeraniol has been suggested to be useful in
protecting patients against the side effects of Bisphosphonates (Ref.).
.
5. Use a dose that is high enough to kill tumours
As the authors describe here and here it is important to use a high enough dose in order to achieve MCS Formulas
anti cancer effectiveness. The dose used in lab experiments was significantly higher compared to
the dose of pitavastatin (up to 4 mg) currently used to treat hypercholesterolaemia. The authors Shop
suggest that an option could be to use cycles of brief (1–2 weeks) high-dose pitavastatin therapy.
This may help to minimise the incidence if myopathy (an issue that may limit the use of statins at
high doses that can result sometimes in rhabodomyolysis).
.
6. Use other inhibitors of mevalonate pathway such as
zoledronic acid
Bisphosphonates such as Zoledronic Acid, are inhibitors of another step in mevalonate pathway.
These drugs are often used to prevent development of bone metastazis in e.g. breast and
prostate cancer patients. I discussed the drug in details here
https://www.cancertreatmentsresearch.com/bisphosphonates/ Recently, it has been shown that
Zoledronic Acid can increase the anti cancer activity of pitavastatin (Ref.). I actually suggested
the combo of Statin and Bisphosphonate in an article I wrote on this website prior to the
publication of this paper (Ref.)
.
plant derived isoprenoids



Isoprenoids are a large family of compounds derived from isopentenyl diphosphate (IPP) and
dimethylallyl diphosphate (DMAPP), therefore partially a result of mevalonate pathway. The Honokiol High Strength
highest variety of plant isoprenoids participate in the interaction of plants with their
environment (Ref.). For example, some are protecting plants against parasites while others are 1. High Strength
responsible for the colours in the plants (such as lycopene). Isoprenoids are known to inhibit 2. Best Purity
3. Increased Absorption
HMGCR (Ref.) This is why it has been previously proposed to be used in combination with
Statins (Ref.). Examples of Isoprenoids that could be useful here to modulate mevalonate
We donate 50% to extend and
pathway are tocotrienols (gamma- and delta-tocotrienol, Vitamin E) (Ref.1, Ref.2) and Lycopene improve life of cancer patients. We
(Ref.), and can be easily found online as food supplements. The anticancer action of Isoprenoids ship World Wide.
may explain the lowered cancer risk (and other cholesterol related diseases) associated with a
diet rich in plant products (Ref.). I would not use Vitamin E during chemo- or radio-therapy, due
to its anti-oxidant properties.
.
Prednisolone: It has been recently published (2019) in another paper co-authored by Dr. Alan
Richardson, that the anti-cancer activity of pitavastatin is potentiated significantly by
prednisolone by augmenting inhibition of the mevalonate pathway (it’s not clear if the inhibition
is due to prednisolone binding to the glucocorticoid receptor, or if prednisolone modulates
SREBP as it has a ring structure mimicking sterols). In this paper, the authors state that the
concentration of prednisolone used in the studies, although relatively high, is comparable to
those clinically achievable using a relatively high dose of prednisolone. As a result, they suggest
that “that it may be appropriate to evaluate the combination of prednisolone and pitavastatin in
clinical trials.” (Ref.)
Many of the findings above have been reported by Dr. Alan Richardson and his team, School of
Pharmacy at Keele University, UK. In a report presented by ScienceDaily, Dr. Alan Richardson stated the
following: “We believe we have found the answer to the paradox: for statins to be effective as a cancer
therapy, the right statin needs to be used, it needs to be delivered at the right dose and interval, and diet
needs to be controlled to reduce sources of geranylgeraniol, which can limit the statin’s effect on cancer
cells.” (Ref.).
Yes, it Works! Successful Case Report in Humans

Here is the article that made me hurry up to write this post as it may help some readers of this website:
“Doctor ‘cancer free’ after Keele University statin test“
The above article is a recent (July 2019) BBC report related to an advanced ovarian cancer patient who
decided to start the experimental treatment proposed by Dr. Alan Richardson.
The patient, Dr Grace Gosar, was a terminal cancer when she started the experiment back in 2018. One
year latter, tests showed no cancer cells present. “As a physician, I know my disease progression and I
thought that I would be in the ground by now,” Dr Gosar said.
The treatment strategy of Dr Grace Gosar, was aligned with Dr. Alan Richardson findings, including
Pitavastatin and a special diet low in geranylgeraniol. Dr. Gosar’s nephew, a biochemist, researched
what foods can be allowed in her diet, and they came up with a diet containing potatoes, tomato paste
and yoghurt.
While this report is at an anecdotal level, I find it very relevant given the fact that it is reported by a
medical doctor (the patient) and a scientist that often publishes it’s work in a recognised journal.
It would be interesting to know what the dose of Pitavastatin was (as I suspect it was a dose >4mg/day)
and if the patient used Zoledronic Acid. I will try to get in contact with the authors.
If any of the readers get in contact with Dr. Alan Richardson and/or have experience with Pitavastatin,
please share that here as it may help others.
Mechanisms
The major mechanism through which Statins are fighting cancer is believed to be related to the
inhibition of HMG CoA-reductase on the mevalonate pathway (Ref.), preventing the synthesis of
cholesterol, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. Other mechanisms related to
anti cancer effects of Statins were also indicated, e.g.:
mitochondria modulation (Ref.)

TGF-β inhibition (Ref.)
T reg cells modulation (Ref.)
Statins are known to inhibit MCT4 (Ref.1, Ref.2, Ref.3)
P-glycoprotein inhibition (Ref.)
Statins Impair Glucose Uptake in Tumor Cells (Ref.)
(Pitavastatin) Reduces inflammation / CRP (Ref.)
inhibition of glutathione peroxidase (GPx)(Ref.), therefore having a pro-oxidant effect
In addition, cholesterol-lowering drugs known as statins have been reported to have significant anti-
inflammatory properties (Ref.).
Side Effects and Toxicity

Statins have long been known to modestly increase levels of hepatic aminotransferases. These
increases often resolve with continued statin therapy. Statins have rarely been associated with severe
hepatic injury.
For toxicity and side effects of Pitavastatin as a function of dose please see the following FDA
document https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022363s000_MedR_P1.pdf
An issue that may limit the use of statins, particularly at high doses, is that statins have been
associated with myopathy and in some cases this can result in rhabodomyolysis. Typically myopathy
presents within a few months after starting or increasing the dose of a statin or after introduction of an
interacting drug. When a patient reports unexplained muscle aches or weakness, it is important for the
clinician to inquire about symptom characteristics. Most commonly, patients present with symptoms
that are distributed proximally (eg, hip flexor region, upper chest and shoulders) and bilaterally.
Nonspecific lower back pain can also be a presenting feature of statin-induced myopathy. (Ref.)
Also read this: Statin Safety and Associated Adverse Events
Inhibition of mevalonate pathway will lead to reduction of CoQ10 since CoQ10 is derived from the
mevalonate pathway (Ref.). This is also the origin of some of the statins side effects. In line with this,
statins side effects may be reduced with the addition of CoQ10 (Ref.).
Note: In a study on Japanese patients, Atorvastatin reduced Coenzyme Q10 level but not Pitavastatin
(Ref.). I think this aspect is very interesting as it may be related to the way they inhibit melavonate
pathway, but I cannot find any paper to explain why this is the case.
Source and Administration

Due to the reasons discussed above, Pitavastatin (Livalo®) is the most suitable statin. Pitavastatin is
available in a generic form so it should be relatively cheap. It should be available at the pharmacy in
most of the countries and released with a prescription.
The maximum dose given for hypercholesterolaemia is 4mg/day. Increasing the dose may come with
side effects as described in this document. As described in this paper, in order to achieve a higher dose
and limit side effects, one idea could be to could be to use cycles of brief (1–2 weeks) high-dose
pitavastatin therapy. This may help avoid side effects such as myopathy that presents a few months
after using high-dose statins. Regardless of the dose, I would take half the dose in the morning and half
the dose in the evening, every 12 hours. I would start with a lower daily dose, e.g. at 2mg/day, for a
cycle of two weeks, and stop taking the drug for the other two weeks (two weeks ON and two weeks
OFF in line with what was suggested in the paper). If the tolerance to the drug is fine, next cycle I would
use 4mg/day (2mg in the morning and 2mg in the evening, 12 hours apart). I would escalate the dose
every cycle to maybe a max of 12-14mg/day, while having in mind that for pitavastatin, there have been
cases of severe myopathy and rhabdomyolysis in clinical trials with doses from 8 mg to 64 mg (Ref.).
During the use pitavastatin, I would also follow a diet that is low in geranylgeraniol. However, for the
latest info on the treatment strategy the best is to have your oncologist contacting Dr. Richardson as
discussed below.
Update August 7th, 2019: I recently contacted Dr. Alan Richardson (author of the papers cited above
(Ref.1, Ref.2) who guided the successful ovarian cancer patient case). For the patient who wishes to try
pitavastatin, Dr. Richardson agrees to be contacted by their oncologist and provide the info required to
start this treatment approach. Dr. Richardson contact details are on the following webpage
https://www.keele.ac.uk/pharmacy-bioengineering/ourpeople/alanrichardson/#biography Dr.
Richardson will help not only with guides on the dose but also on the suitable diet focused on foods that
do not contain geranylgeraniol.
If Pitavastatin is not available, the next option in my view is Atorvastatin. Typically, cancer patients use
Atorvastatin 40mg/day for the first 2 weeks, followed by 80mg/day thereafter. The daily dose should
also be split in two, morning and evening.
Lovastatin’s absorption increases when taken with food, whereas absorption of atorvastatin, fluvastatin,
and pravastatin decreases when taken with food. Simvastatin and rosuvastatin are not affected by food
intake http://www.medscape.com/viewarticle/561128
Others
Lovastatin & Interferon – this is a very interesting treatment strategy, patented and performed at a
clinic in US, with an outcome that seems to be impressive. I do not know anybody who was treated at
this clinic.
New interferon/lovastatin treatment to battle cancer

patent
References
Statin drugs to reduce breast cancer recurrence and mortality
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247616/
Epidemiologic studies have, variably, shown the concomitant use of statin drugs to be beneficial to
cancer outcomes. Statin drugs have been FDA approved for three decades for the treatment of high
cholesterol and atherosclerotic coronary artery disease and are widely used. This has engendered
studies as to their influence on concomitant diseases, including cancers. In this context, statin use has
been correlated, variably, with a decrease in deaths from breast cancer. However, there is no extant
model for this effect, and the extent of efficacy is open to question.
The overarching goal of this article is to communicate to the reader of the potential of statins to reduce
breast cancer progression and mortality. This is the use as a secondary prevention measure, and not as
a therapy to directly counter active cancer. First, salient aspects of statin pharmacology, as relates to
cardiovascular disease, will be discussed. Second, the basic and clinical research studies that
investigate statin usage in breast cancer will be presented. Additionally, statin effects in other cancer
types will be included for context. Finally, proposals for future basic and clinical research studies to
determine the role of statins in breast cancer management will be presented.
The poor design of clinical trials of statins in oncology may explain their failure – Lessons for drug
repurposing https://www.ncbi.nlm.nih.gov/pubmed/29936313
Statins are widely used to treat hypercholesterolaemia. However, by inhibiting the production of
mevalonate, they also reduce the production of several isoprenoids that are necessary for the function
of small GTPase oncogenes such as Ras. As such, statins offer an attractive way to inhibit an
“undruggable” target, suggesting that they may be usefully repurposed to treat cancer. However, despite
numerous studies, there is still no consensus whether statins are useful in the oncology arena.
Numerous preclinical studies have provided evidence justifying the evaluation of statins in cancer
patients. Some retrospective studies of patients taking statins to control cholesterol have identified a
reduced risk of cancer mortality. However, prospective clinical studies have mostly not been successful.
We believe that this has occurred because many of the prospective clinical trials have been poorly
designed. Many of these trials have failed to take into account some or all of the factors identified in
preclinical studies that are likely to be necessary for statins to be efficacious. We suggest an improved
trial design which takes these factors into account. Importantly, we suggest that the design of clinical
trials of drugs which are being considered for repurposing should not assume it is appropriate to use
them in the same way as they are used in their original indication. Rather, such trials deserve to be
informed by preclinical studies that are comparable to those for any novel drug.
An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer

https://www.ncbi.nlm.nih.gov/pubmed/31023626
OBJECTIVE: The statin family of cholesterol-lowering drugs has been shown to induce tumor-specific

apoptosis by inhibiting the rate-limiting enzyme of the mevalonate (MVA) pathway, HMG-
CoA reductase (HMGCR). Accumulating evidence suggests that statin use may delay
prostate cancer (PCa) progression in a subset of patients; however, the determinants of statin drug
sensitivity in PCa remain unclear. Our goal was to identify molecular features of statin-sensitive PCa
and opportunities to potentiate statin-induced PCa cell death.
METHODS: Deregulation of HMGCR expression in PCa was evaluated by immunohistochemistry. The

response of PCa cell lines to fluvastatin-mediated HMGCR inhibition was assessed using cell viability
and apoptosis assays. Activation of the sterol-regulated feedback loop of the MVA pathway, which was
hypothesized to modulate statin sensitivity in PCa, was also evaluated. Inhibition of this statin-induced
feedback loop was performed using RNA interference or small molecule inhibitors. The achievable
levels of fluvastatin in mouse prostate tissue were measured using liquid chromatography-mass
spectrometry.
RESULTS: High HMGCR expression in PCa was associated with poor prognosis; however, not all PCa cell
lines underwent apoptosis in response to treatment with physiologically-achievable concentrations of
fluvastatin. Rather, most cell lines initiated a feedback response mediated by sterol regulatory element-
binding protein 2 (SREBP2), which led to the further upregulation of HMGCR and other lipid metabolism
genes. Overcoming this feedback mechanism by knocking down or inhibiting SREBP2 potentiated
fluvastatin-induced PCa cell death. Notably, we demonstrated that this feedback loop is
pharmacologically-actionable, as the drug dipyridamole can be used to block fluvastatin-induced
SREBP activation and augment apoptosis in statin-insensitive PCa cells.
CONCLUSION: Our study implicates statin-induced SREBP2 activation as a PCa vulnerability that can be
exploited for therapeutic purposes using clinically-approved agents.
Statin use is associated with improved survival in patients undergoing surgery for renal cell carcinoma
https://www.sciencedirect.com/science/article/abs/pii/S1078143914003500?via%3Dihub
Conclusions: These data suggest that statin usage at time of surgery is independently associated with
improved OS and DSS in patients undergoing surgery for RCC.
Statin Use and Reduced Cancer-Related Mortality

https://www.nejm.org/doi/full/10.1056/NEJMoa1201735
BACKGROUND: A reduction in the availability of cholesterol may limit the cellular proliferation required
for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer
diagnosis is associated with reduced cancer-related mortality.
METHODS: We assessed mortality among patients from the entire Danish population who had received
a diagnosis of cancer between 1995 and 2007, with follow-up until December 31, 2009. Among patients
40 years of age or older, 18,721 had used statins regularly before the cancer diagnosis and 277,204 had
never used statins.
RESULTS: Multivariable-adjusted hazard ratios for statin users, as compared with patients who had
never used statins, were 0.85 (95% confidence interval [CI], 0.83 to 0.87) for death from any cause and
0.85 (95% CI, 0.82 to 0.87) for death from cancer. Adjusted hazard ratios for death from any cause
according to the defined daily statin dose (the assumed average maintenance dose per day) were 0.82
(95% CI, 0.81 to 0.85) for a dose of 0.01 to 0.75 defined daily dose per day, 0.87 (95% CI, 0.83 to 0.89)
for 0.76 to 1.50 defined daily dose per day, and 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50 defined
daily dose per day; the corresponding hazard ratios for death from cancer were 0.83 (95% CI, 0.81 to
0.86), 0.87 (95% CI, 0.83 to 0.91), and 0.87 (95% CI, 0.81 to 0.92). The reduced cancer-related mortality
among statin users as compared with those who had never used statins was observed for each of 13
cancer types.
CONCLUSIONS: Statin use in patients with cancer is associated with reduced cancer-related mortality.
This suggests a need for trials of statins in patients with cancer.
Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell
carcinoma: impact on prognosis, cell-cycle progression and proliferation.
Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and
reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug
repurposing approaches with these substances in RCC appear warranted.
Statin Use Shows Increased Overall Survival in Patients Diagnosed With Pancreatic Cancer: A Meta-
Analysis https://www.ncbi.nlm.nih.gov/pubmed/30973465
Statin-dependent modulation of mitochondrial metabolism in cancer cells is independent of

cholesterol content https://www.ncbi.nlm.nih.gov/pubmed/30951369
Statins, widely used to treat hypercholesterolemia, inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A

reductase, the rate-limiting enzyme of de novo cholesterol (Chol) synthesis. Statins have been also
reported to slow tumor progression. In cancer cells, ATP is generated both by glycolysis and oxidative
phosphorylation. Mitochondrial membrane potential (ΔΨ), a readout of mitochondrial metabolism, is
sustained by the oxidation of respiratory substrates in the Krebs cycle to generate NADH and flavin
adenine dinucleotide, which are further oxidized by the respiratory chain. Here, we studied the short-
term effects of statins (3-24 h) on mitochondrial metabolism on cancer cells. Lovastatin (LOV) and
simvastatin (SIM) increased ΔΨ in HepG2 and Huh7 human hepatocarcinoma cells and HCC4006
human lung adenocarcinoma cells. Mitochondrial hyperpolarization after LOV and SIM was dose and
time dependent. Maximal increase in ΔΨ occurred at 10 µM and 24 h for both statins. The structurally
unrelated atorvastatin also hyperpolarized mitochondria in HepG2 cells. Cellular and mitochondrial Chol
remained unchanged after SIM. Both LOV and SIM decreased basal respiration, ATP-linked respiration,
and ATP production. LOV and SIM did not change the rate of lactic acid production. In summary, statins
modulate mitochondrial metabolism in cancer cells independently of the Chol content in cellular
membranes without affecting glycolysis.
Statin drugs to reduce breast cancer recurrence and mortality

Epidemiologic studies have, variably, shown the concomitant use of statin drugs to be beneficial to
cancer outcomes. Statin drugs have been FDA approved for three decades for the treatment of high
cholesterol and atherosclerotic coronary artery disease and are widely used. This has engendered
studies as to their influence on concomitant diseases, including cancers. In this context, statin use has
been correlated, variably, with a decrease in deaths from breast cancer. However, there is no extant
model for this effect, and the extent of efficacy is open to question.The overarching goal of this article
is to communicate to the reader of the potential of statins to reduce breast cancer progression and
mortality. This is the use as a secondary prevention measure, and not as a therapy to directly counter
active cancer. First, salient aspects of statin pharmacology, as relates to cardiovascular disease, will be
discussed. Second, the basic and clinical research studies that investigate statin usage in breast cancer
will be presented. Additionally, statin effects in other cancer types will be included for context. Finally,
proposals for future basic and clinical research studies to determine the role of statins in breast cancer
management will be presented.
Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a
Belgian population-based study. https://www.ncbi.nlm.nih.gov/pubmed/30820714
In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was
associated with a decreased mortality.
Curbing Lipids: Impacts ON Cancer and Viral Infection https://www.ncbi.nlm.nih.gov/pubmed/30717356
Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include
signaling, storing energy, and acting as the central structural component of cell membranes. Alteration
of lipid metabolism is a prominent feature of cancer, as cancer cells must modify their metabolism to
fulfill the demands of their accelerated proliferation rate. This aberrant lipid metabolism can affect
cellular processes such as cell growth, survival, and migration. Besides the gene mutations,
environmental factors, and inheritance, several infectious pathogens are also linked with human
cancers worldwide. Tumor viruses are top on the list of infectious pathogens to cause human cancers.
These viruses insert their own DNA (or RNA) into that of the host cell and affect host cellular processes
such as cell growth, survival, and migration. Several of these cancer-causing viruses are reported to be
reprogramming host cell lipid metabolism. The reliance of cancer cells and viruses on lipid metabolism
suggests enzymes that can be used as therapeutic targets to exploit the addiction of infected diseased
cells on lipids and abrogate tumor growth. This review focuses on normal lipid metabolism, lipid
metabolic pathways and their reprogramming in human cancers and viral infection linked cancers and
the potential anticancer drugs that target specific lipid metabolic enzymes. Here, we discuss statins
and fibrates as drugs to intervene in disordered lipid pathways in cancer cells. Further insight into the
dysregulated pathways in lipid metabolism can help create more effective anticancer therapies.
Statins enhance efficacy of venetoclax in blood cancers

Statins have shown promise as anticancer agents in experimental and epidemiologic research. However,
any benefit that they provide is likely context-dependent, for example, applicable only to certain cancers
or in combination with specific anticancer drugs. We report that inhibition of 3-hydroxy-3-
methylglutaryl coenzyme A reductase (HMGCR) using statins enhances the proapoptotic activity of the
B celllymphoma-2 (BCL2) inhibitor venetoclax (ABT-199) in primary leukemia and lymphoma cells but
not in normal human peripheral blood mononuclear cells. By blocking mevalonate production, HMGCR
inhibition suppressed protein geranylgeranylation, resulting in up-regulation of proapoptotic protein p53

up-regulated modulator of apoptosis (PUMA). In support of these findings, dynamic BH3 profiling
confirmed that statins primed cells for apoptosis. Furthermore, in retrospective analyses of three
clinical studies of chronic lymphocytic leukemia, background statin use was associated with enhanced
response to venetoclax, as demonstrated by more frequent complete responses. Together, this work
provides mechanistic justification and clinical evidence to warrant prospective clinical investigation of
this combination in hematologic malignancies.
Association between statins and prostate tumor inflammatory infiltrate in men undergoing radical
prostatectomy. https://www.ncbi.nlm.nih.gov/pubmed/20160265/
Given previous reports that inflammation is associated with advanced prostate cancer, and statin use is
associated with decreased prostate cancer progression risk, our findings suggest that inhibition of
inflammation within tumors may be a potential mechanism for purported anti-prostate cancer
properties of statins.
Statins and prostate cancer: role of cholesterol inhibition vs. prevention of small GTP-binding proteins
Prostate cancer (PCa) is initially regulated by androgens, such as testosterone and dihydrotestosterone,
which regulates cell proliferation and survival by activating the androgen receptor (AR), but later
progresses to an aggressive, metastatic, androgen-independent stage for which, currently, there is no
cure. Here, we argue that prevention of PCa progression is a better strategy compared to trying to cure
the disease once it has already progressed. Statins inhibit the mevalonate pathway, thus preventing the
synthesis of cholesterol, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. Multiple clinical
studies have shown an inverse relationship between statin use and PCa risk, especially the risk for
developing advanced metastatic cancer. Biochemical investigations have largely corroborated the
positive effect of statins on PCa risk, showing that statins inhibited cell proliferation, induced apoptosis,
and decreased cell migration and invasion in PCa cells in vitro. However, investigations of the
biochemical mechanism of statin action in preventing advanced/high risk PCa remains inconclusive, as
statins can act through cholesterol, geranylgeranyl, or farnesyl mediated signals. This review discusses
the current clinical and biochemical findings on the use of statins in preventing PCa. Evidence of statin
action through cholesterol as well as geranylgeranylation and farnesylation has been discussed. As
cholesterol is a precursor of androgen production, it can reduce PCa risk by decreasing the levels of
circulating testosterone, which in turn reduces the levels of interprostatic dihydrotestosterone, a strong
ligand for the AR. Cholesterol was also shown to accumulate in lipid rafts and regulate the activation of
the phosphatidylinositol 3-kinase/Akt pathway. However, clinical evidence from multiple studies also
point to the existence of cholesterol-independent pathways mediating statin action in PCa patients. In
particular, ligand-activated AR activation is seen in early stage PCa and activation of the cholesterol
pathway did not indicate an effect on metastasis. Cell migration and invasion, on the other hand, is
regulated strongly by members of the Ras superfamily of small GTPases, especially the Rho family,
which is geranylgeranylated. This review, therefore, also compares the effects of statins on both
cholesterol and geranylgeranylated and farnesylated small GTPases regulating tumor progression and
metastasis in biochemical and clinical studies.
Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer
metastasis https://www.tandfonline.com/doi/full/10.1080/15384047.2016.1219817
The isoprenoid biosynthetic pathway (IBP) plays a critical role in providing substrates and enzymes
necessary for the post-translational modification and thus activation of a number of proteins involved
in prostate cancer metastasis. Previous work by our lab found novel compound disodium
[(6Z,11E,15E)-9-[bis(sodiooxy)phosphoryl]−17-hydroxy-2,6,12,16-tetramethyheptadeca-2,6,11,15-
tetraen-9-yl]phosphonate (GGOHBP), which inhibits the IBP enzyme geranylgeranyl diphosphate
synthase (GGDPS), reduced protein geranylgeranylation without altering protein farnesylation. This
activity significantly reduced adrenal gland tumor burden in a murine model of human prostate cancer
metastasis which relied on treatment of established disease. The present study determined the ability
of GGDPS inhibition to slow the development of prostate cancer metastasis in a preventative murine
model. Using tail vein injection of human derived PC-3 prostate cancer cells 4 d after initiating daily
GGOHBP or vehicle treatments, we found GGOHBP significantly reduced whole body tumor burden,
significantly slowed the development of tumors, and prolonged overall survival as compared to vehicle
treated animals. The observed reduction in soft tissue tumor burden corresponded to a biochemical
reduction in Rap1A geranylgeranylation, which for prostate cancer is important in its own merit and
which serves as a surrogate marker for Rho family, i.e. Rac, protein modification. This effect was
present in all treated mice pointing to strong target engagement, which was not observed in non-tumor
burdened tissues or control mice. Our findings reiterate a role for protein geranylgeranylation in the
development of prostate cancer metastasis in vivo.
Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant
ovarian cancer https://www.nature.com/articles/s41598-017-05595-4
Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have
suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to
demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic
statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone
clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A
reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and
upregulated by mutated TP53, a gene commonly altered in ovarian cancer. Pitavastatin-induced
apoptosis was blocked by geranylgeraniol and mevalonate, products of the HMGCR pathway, confirming
that pitavastatin causes cell death through inhibition of HMGCR. Solvent extracts of human and mouse
food were also able to block pitavastatin-induced apoptosis, suggesting diet might influence the
outcome of clinical trials. When nude mice were maintained on a diet lacking geranylgeraniol, oral
pitavastatin caused regression of Ovcar-4 tumour xenografts. However, when the animal diet was
supplemented with geranylgeraniol, pitavastatin failed to prevent tumour growth. This suggests that a
diet containing geranylgeraniol can limit the anti-tumour activity of pitavastatin and diet should be
controlled in clinical trials of statins.
Ovarian cancer: Statins might be effective with diet control

https://www.medicalnewstoday.com/articles/318453.php
Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells
https://www.nature.com/articles/s41598-017-08649-9
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously
shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether
the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase
inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with
zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6–
14 μM), zoledronic acid (IC50 = 21–57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM)
inhibited the growth of ovarian cancer cell cultures. Combinations of pitavastatin with zoledronic acid
displayed additive or synergistic effects in cell growth assays in 10 of 11 cell lines evaluated as well as
in trypan blue exclusion, cellular ATP or caspase 3/7, 8 and 9 assays. Pitavastatin reduced levels of
GGT-IIβ and the membrane localization of several small GTPases and this was potentiated by zoledronic
acid. siRNA to GGT-Iβ and GGT-IIβ used in combination, but not when used individually, significantly
increased the sensitivity of cells to pitavastatin. These data suggest that zoledronic acid, a drug already
in clinical use, may be usefully combined with pitavastatin in the treatment of ovarian cancer.
Statins could ease coughing in lung disease patients, study finds

https://www.sciencedaily.com/releases/2014/03/140324111554.htm
Statins improve the anti-tumor effects of ACLY inhibition

http://onlinelibrary.wiley.com/doi/10.1002/jcp.22895/abstract
Atorvastatin Decreases the Coenzyme Q10 Level in the Blood of Patients at Risk for Cardiovascular
Disease and Stroke https://jamanetwork.com/journals/jamaneurology/fullarticle/786017
Background Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for

the treatment of hypercholesterolemia and coronary heart disease and for the prevention of stroke.
There have been various adverse effects, most commonly affecting muscle and ranging from myalgia to
rhabdomyolysis. These adverse effects may be due to a coenzyme Q10 (CoQ10) deficiency because
inhibition of cholesterol biosynthesis also inhibits the synthesis of CoQ10.
Objective To measure CoQ10 levels in blood from hypercholesterolemic subjects before and after
exposure to atorvastatin calcium, 80 mg/d, for 14 and 30 days.
Design Prospective blinded study of the effects of short-term exposure to atorvastatin on blood levels
of CoQ10.
Setting Stroke center at an academic tertiary care hospital.
Patients We examined a cohort of 34 subjects eligible for statin treatment according to National
Cholesterol Education Program: Adult Treatment Panel III criteria.
Results The mean ± SD blood concentration of CoQ10 was 1.26 ± 0.47 µg/mL at baseline, and
decreased to 0.62 ± 0.39 µg/mL after 30 days of atorvastatin therapy (P<.001). A significant decrease
was already detectable after 14 days of treatment (P<.001).
Conclusions Even brief exposure to atorvastatin causes a marked decrease in blood

CoQ10 concentration. Widespread inhibition of CoQ10 synthesis could explain the most commonly
reported adverse effects of statins, especially exercise intolerance, myalgia, and myoglobinuria.
Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer

Pure and mixed isoprenoid end products of plant mevalonate metabolism trigger actions that suppress
3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity. These actions modulate HMG
CoA reductase mRNA translation and the proteolytic degradation of HMG CoA reductase. Such post-
transcriptional events, we propose, are activated directly by acyclic isoprenoids and indirectly by cyclic
isoprenoids. Isoprenoids, acting secondarily to the dominant transcriptional effector of sterologenesis,
modestly lower cholesterol levels, if and only if, sterologenesis is not repressed by a saturating imput of
dietary cholesterol. An anomaly associated with tumor growth-a sterol feedback-resistant HMG CoA
reductase activity-ensures a pool of sterologenic pathway intermediates. Such intermediates provide
lipophilic anchors essential for membrane attachment and biological activity of growth hormone
receptors, nuclear lamins A and B, and oncogenic ras. Tumor HMG CoA reductase retains high
sensitivity to the isoprenoid-mediated secondary regulation. Repression of mevalonate synthesis by
plant-derived isoprenoids reduces ras and lamin B processing, arrests cells in G1, and initiates cellular
apoptosis. This unique tumor cell-specific sensitivity allows isoprenoids to be used for tumor therapy,
an application emulating that of the statins, but one free of adverse effects. When evaluated at levels
provided by a typical diet, isoprenoids individually have no impact on cholesterol synthesis and tumor
growth. Nonetheless, isoprenoid-mediated activities are additive, and, sometimes synergistic.
Therefore, the combined actions of the estimated 23,000 isoprenoid constituents of plant materials,
acting in concert with other chemopreventive phytochemicals, may explain the lowered cancer risk
associated with a diet rich in plant products. In contrast, that lowering of cancer risk does not
correspond to supplemental intake of other dietary factors associated with fruits, vegetables, and cereal
grains, namely fiber, beta-carotene, vitamin C, and vitamin E, and only weakly to supplemental folate.
Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy

and chemoprevention https://www.ncbi.nlm.nih.gov/pubmed/15229351/
Pools of farnesyl diphosphate and other phosphorylated products of the mevalonate pathway are
essential to the post-translational processing and physiological function of small G proteins, nuclear
lamins, and growth factor receptors. Inhibitors of enzyme activities providing those pools, namely, 3-
hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and mevalonic acid-pyrophosphate
decarboxylase, and of activities requiring substrates from the pools, the prenyl protein transferases,
have potential for development as novel chemotherapeutic agents. Their potentials as suggested by the
clinical responses recorded in Phase I and II investigations of inhibitors of HMG CoA reductase (the
statins), of mevalonic acid-pyrophosphate decarboxylase (sodium phenylacetate and sodium
phenylbutyrate), and of farnesyl protein transferase (R115777, SCH66336, BMS-214662, Tipifarnib, L-
778,123, and, prematurely, perillyl alcohol) are dimmed by dose-limiting toxicities. These
nondiscriminant growth-suppressive agents induce G1 arrest and initiate apoptosis and differentiation,
effects attributed to modulation of cell signaling pathways either by modulating gene expression,
suppressing the post-translational processing of signaling proteins and growth factor receptors, or
altering diacylglycerol signaling. Diverse isoprenoids and the HMG CoA reductase inhibitor, lovastatin,
modulate cell growth, induce cell cycle arrest, initiate apoptosis, and suppress cellular signaling
activities. Perillyl alcohol, the isoprenoid of greatest clinical interest, initially was considered to inhibit
farnesyl protein transferase; follow-up studies revealed that perillyl alcohol suppresses the synthesis of
small G proteins and HMG CoA reductase. In sterologenic tissues, sterol feedback control, mediated by
sterol regulatory element binding proteins (SREBPs) 1a and 2, exerts the primary regulation on HMG
CoA reductase activity at the transcriptional level. Secondary regulation, a nonsterol isoprenoid-
mediated fine-tuning of reductase activity, occurs at the levels of reductase translation and
degradation. HMG CoA reductase activity in tumors is elevated and resistant to sterol feedback
regulation, possibly as a consequence of aberrant SREBP activities. Nonetheless, tumor reductase
remains sensitive to isoprenoid-mediated post-transcriptional downregulation. Farnesol, an acyclic
sesquiterpene, and farnesyl homologs, gamma-tocotrienol and various farnesyl derivatives, inhibit
reductase synthesis and accelerate reductase degradation. Cyclic monoterpenes, d-limonene, menthol
and perillyl alcohol and beta-ionone, a carotenoid fragment, lower reductase mass; perillyl alcohol and
d-limonene lower reductase mass by modulating translational efficiency. The elevated reductase
expression and greater demand for nonsterol products to maintain growth amplify the susceptibility of
tumor reductase to isoprenoids, therein rendering tumor cells more responsive than normal cells to
isoprenoid-mediated growth suppression. Blends of lovastatin, a potent nondiscriminant inhibitor of
HMG CoA reductase, and gamma-tocotrienol, a potent isoprenoid shown to post-transcription-ally
attenuate reductase activity with specificity for tumors, synergistically affect the growth of human
DU145 and LNCaP prostate carcinoma cells and pending extensive preclinical evaluation, potentially
offer a novel chemotherapeutic strategy free of the dose-limiting toxicity associated with high-dose
lovastatin and other nondiscriminant mevalonate pathway inhibitors.
Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its
restorative feedback loop https://www.ncbi.nlm.nih.gov/pubmed/24994712
New therapies are urgently needed for hematologic malignancies, especially in patients with relapsed
acute myelogenous leukemia (AML) and multiple myeloma. We and others have previously shown that
FDA-approved statins, which are used to control hypercholesterolemia and target the mevalonate
pathway (MVA), can trigger tumor-selective apoptosis. Our goal was to identify other FDA-approved
drugs that synergize with statins to further enhance the anticancer activity of statins in vivo. Using a
screen composed of other FDA approved drugs, we identified dipyridamole, used for the prevention of
cerebral ischemia, as a potentiator of statin anticancer activity. The statin-dipyridamole combination
was synergistic and induced apoptosis in multiple myeloma and AML cell lines and primary patient
samples, whereas normal peripheral blood mononuclear cells were not affected. This novel combination
also decreased tumor growth in vivo. Statins block HMG-CoA reductase (HMGCR), the rate-limiting
enzyme of the MVA pathway. Dipyridamole blunted the feedback response, which upregulates HMGCR
and HMG-CoA synthase 1 (HMGCS1) following statin treatment. We further show that dipyridamole
inhibited the cleavage of the transcription factor required for this feedback regulation, sterol regulatory
element-binding transcription factor 2 (SREBF2, SREBP2). Simultaneously targeting the MVA pathway
and its restorative feedback loop is preclinically effective against hematologic malignancies. This work
provides strong evidence for the immediate evaluation of this novel combination of FDA-approved drugs
in clinical trials.
Feedback Regulation of Cholesterol Synthesis

HMG CoA reductase produces mevalonate, an important intermediate in the synthesis of cholesterol
and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback
control through multiple mechanisms that are mediated by sterol and nonsterol end-products of
mevalonate metabolism. Here, I will discuss recent advances that shed light on one mechanism for
control of reductase, which involves rapid degradation of the enzyme. Accumulation of certain sterols
triggers binding of reductase to endoplasmic reticulum (ER) membrane proteins called Insig-1 and
Insig-2. Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase
called gp78, which initiates ubiquitination of reductase. This ubiquitination is an obligatory reaction for
recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes. Thus,
sterol accelerated degradation of reductase represents an example of how a general cellular process
(ER-associated degradation) is used to control an important metabolic pathway (cholesterol synthesis).
Disclaimer
This site is not designed to and does not provide medical advice, professional diagnosis, opinion,
treatment or services to you or to any other individual. Through this site and linkages to other sites, I
provide general information for educational purposes only. The information provided in this site, or
through linkages to other sites, is not a substitute for medical or professional care, and you should not
use the information in place of a visit, call consultation or the advice of your physician or other
healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any
other information, services or product you obtain through this site. This is just my own personal opinion
regarding what we have learned on this road.
Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?

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 CANCER TYPES, CHOLESTEROL MODULATION, OVARIAN CANCER, TREATMENT STRATEGIES

 34 COMMENTS
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34 thoughts on “Making Cholesterol-Lowering Statin

Drugs More Effective Against Cancer”
Shanti
JULY 22, 2019 AT 2:42 AM
Bless you Daniel, you are on holiday and still you take the time to think of all of us on the battlefield with
cancer _/\_ and to get this important information to us. Thank you.
REPLY
johan
JULY 22, 2019 AT 3:34 AM
This story with statins just keeps getting better! Hope readers share this article far and wide!
REPLY
Inabari
JULY 22, 2019 AT 5:31 PM
As a statin user for the lymphoma, i appreciate a lot this post Daniel, and especially while on vacation.
Thank you
REPLY
Daniel 
JULY 22, 2019 AT 8:34 PM
Dear Inabari, when writing this post I also had in mind your question here
https://www.cancertreatmentsresearch.com/community/lymphoma/please-help-with-new-strategy-
refractory-hodgkin-lymphoma/paged/2/#post-1065
I hope this answers your question. Like I said in the post, I will try to get in contact with the
scientists and see if I can get info on the dose used by the ovarian cancer patient. If I learn more, I
will let you know.
Kind regards,
Daniel
REPLY
Daniel 
JULY 22, 2019 AT 8:31 PM
Dear Friends, thank you for your support.
REPLY
marcosbomber901
JULY 22, 2019 AT 10:11 PM
Daniel really are one of the most fabulous people I know, your work for others and your commitment to
those who need your help is priceless, I was already applying the statins but not pivastatin but
atorvastaatina, I do not know this last study. soon write again I am now very busy I still confirm
something but will be good news
REPLY
Daniel 
JULY 22, 2019 AT 10:45 PM
Hi Marcos, thanks a lot. That applies to you and many of our friends discussing here. I very much
believe that. Good news sounds great! I am looking forward to know more whenever you have time.
All the best!
REPLY
Jcancom
JULY 23, 2019 AT 3:14 AM
D, another Good One! It is just one after another after another! All with stage IV patient reports that
recovered using these treatments!
I really think that we need to have a post that brings it all together in one place. Most patients are just
so totally overwhelmed by it all, that they can be in a state of shock while they try and put everything
together. What we need to do for them is make it easy by giving a list of about 20 treatments are easily
available, proven safe and with evidence of human efficacy. Right off the top we could include:
silver, FB, statins etc. . This would make things a great deal easier for them and allow them to be more
automatic than become stuck in paralysis through analysis. The one tricky thing might be finding the
half-lives of the different treatments.
D, remember if you go to the beach to wear sun-screen! There is a European nation that I prefer not to
identify that is notorious for racing out into the sun, only to develop bad sun burns from overexposure.
Be sun safe! J
REPLY
kp
AUGUST 22, 2019 AT 8:37 PM
Thank you Daniel.
This past summer I picked up a book called “How to Starve Cancer” by Jane McLelland from the UK. I
don’t know if her book has been mentioned on your site. At age 35 she battled cervical cancer in 1992,
then 7 years later lung cancer in 1999. By that time, she had enough and decided there had to be more
than just chemo, radiation, and surgery. She is a strong advocate on Berberine (leading to Metformin), a
dewormer…not specifically the dog kind, and also statins. Now at age 63 she is thriving. Diet (no
sugar), tons of supplements, exercise, stress relief exercises. This is starting to parallel what others are
now finding to do. Hope this helps!
REPLY
Daniel 
AUGUST 23, 2019 AT 12:52 AM
Hi KP,
Thanks a lot! We did discussed shortly Jane’s book and strategy to fight cancer, which is very much
appreciated. However, we still need to adapt these strategies to our case. For example, given that
you are doing immuno-therapy now, I would not take antibiotics that are are also part of Jane’s
strategy. There was a recent study showing that antibiotics strongly decrease the effectiveness of
immuno therapies such as anti-PD1/PDL1. On the other hand, there are other studies cited in the
links I sent to you earlier, indicating that probiotics strongly increase the effectiveness of the
immuno-therapies. Beyond antibiotics, metabolic treatments have to be carefully considered when
combined with immuno therapies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340776/ So,
when doing immuno therapy, I would better stop the metabolic treatment and instead focus on a
strategy to support the immune action. Such approach would include the pH strategy from the link I
sent to you earlier https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-
strategy/, as well as drugs such as Cimetidine to reduce Tregs and MSDC
https://www.cancertreatmentsresearch.com/case-report-stage-iv-sarcoma-good-news-from-jg/,
COX-1 and COX-2 inhibitor drugs such as Celecoxib, Vitamin D3, mushrooms such as Coriollus, Beta
Glucan.
Kind regards,
Daniel
REPLY
kp
AUGUST 23, 2019 AT 2:16 AM
Daniel,
Need some clarification. I don’t think I’m taking any antibiotics. I take a statin for cholesterol as
prescribed by my MD Internist.
Also the Berberine since I found out it definitely stopped then bleeding of my masses and prevented my
hemoglobin to drop. The other supplements are prescribed by my Integrative Dr. Keith Block..of the
Block Center. He found out that a lot of people having to go back on chemo were subjects of chemo that
was given too fast , too high of a dose…made the cancer come back even worse. As was my case with
my first round. He started the center in the 80’s and have helped people live past their due date (which
he doesn’t believe in). Some of the supplements are milk thistle, cucurmin, fish oil, etc. So yes…no
antibiotics. Not sure about the aspirin bit.
Thanks for your help.
kp
REPLY
kapil.agrawalkapil
SEPTEMBER 10, 2019 AT 12:50 PM
Hi Daniel – I must say this is a GEM of a post!
I have myself tried to read and dive deeper into the Cholestrol pathway but have not been able to get to
this level of actionable detail.
My sense is that Mevalonate pathway is also expressed in Triple Negative Breast Cancer (Ref Jane’s
Book). I have few questions though.
1. My Mother is currently on IV Chemo: Lipodox and Cyclophosphamide. Could Pitavastatin be added

with Chemo concurrently?
2. What would be advisable dose and frequency to get anti-cancer benefits.
3. I realized that Geranylgeraniol is also present in Olive Oil, Flaxseed Oil and rice. My Mother takes Olive
Oil (with Turmeric and black pepper to boost curcumin absorption) and occasionally eats rice as well.
Would have to now look for alternatives.
Again great work and very solid research. Keep it up (Thumbs up)
REPLY
Daniel 
Dear Kapil,
Thank you for the positive feedback.
I very much believe that Mevalonate pathway is key weak point for most tumor types including TNBC. In my view, it’s at the
same level as the strategy to kill tumours via energy depletion (inhibiting glyco and mitho), via pH modulation, via inhibition of
anti-oxidant production. It’s because of it’s impact on both cholesterol and Ras and Rho pathways, essential in cancer.
An extension of this strategy is discussed here https://www.cancertreatmentsresearch.com/reduce-cholesterol-in-cancer-

cells-to-fight-cancer/
Lipodox is Doxorubicin. This is weak base. This would make me think that the pH strategy would work very well in combo with
Doxo
https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ as it would increase Doxo absorption by

cancer cells. But the issue is that on the other hand Cyclo is weak acid … What is the frequency of the two and how are they
taken in respect to each other?
Based on the interaction checker, there is no interaction between Pitavastatin and the two chemos.
https://reference.medscape.com/drug-interactionchecker?
pa=8nH27%2FYeS0vA8eF6F2nbnQB1sYC0K6JDtmEJ9GvjXpGKjyR8pb5zhFHWxFAVqnXqVrJxKJt4DRD8mxYr6kYfOw%3D%3D
For discussion on dose and frequency for Pitavastatin as well as bet diet, please contact Dr. Alan Richardson. He will help you
and your oncologist, I expect for free. If there is no response, please let me know and I will have a response for you.
Please note that Dr. Richardson prefers not to combine Pitavastatin with anything else that further lowers cholesterol other
than the diet (that excludes geranylgeranyol) as he believes that the Statin kills tumor cells due to inhibition of Ras and Rho
related pathways, as a result of depletion of geranylgeranyl and geranylgeraniol (that can be converted in geranylgeranyl via
the salvage pathway). However, when I discussed with him, he was triggered by the idea of inhibiting ACLYL (using HCA
supplement) that is located upstream HMGCR (inhibited by statins).
He did not explain why he doesn’t like adding extra cholesterol inhibitors but I think he probably thinks that by inhibiting even
more cholesterol, there may be unknown feedback mechanism activated in the cell, to upregulate melavonate pathway, which
in turn would lower the effectiveness of Statins.
Kind regards,
Daniel
REPLY
kapil.agrawalkapil 
Hey Daniel – I cannot thank you enough for your detailed and comprehensive as well as such
timely responses.
My Mother is getting Lipodox along with a big dose of Cyclophosphamide every 3 weeks. She
also gets Zoldria (Zoledronic Acid which is a type of Bisphosphonate) with these two drugs.
We have started her on 2mg * 2 (morning and evening) on Pitavastatin from today. Would you
know if it is best taken with food or on empty stomach. Based on your discussion with Dr.
Richardson, I hope he is fine with Zoldria being given as the primary idea of Zoldria is to address
the bone lesion.
REPLY
Daniel 
Hi Kapil,
You are very welcome. I think I would start with a total of 2mg first divided in two (1mg in
the morning and 1mg in the evening). Starting with 4mg in total may lead to side effects
faster – I would start with 4mg/day dose (as I understand you do now) only if I would feel I
need response as soon as possible.
To my knowledge, it can be taken with or withouth food.
In my view the addition of Bisphosphonates is perfect since it inhibits an enzyme (FPPS)

located just upstream FPP and GGPP.
Kind regards,
Daniel
REPLY
nathalie G 
JANUARY 16, 2020 AT 12:45 AM
Hello,
Sorry, I’n not sure to understand. So, finally, Metformin coud be counter productiv with
Pitavastatin ??? “Dr Richardson prefers not combin to Pitavastatin with anything else”.
And you mention prednisolone and other things (Zoldria, Mebendazole…), but you don’t
mention Metformine on this page…
Pitavastatin is difficult to get, maybe here if we can trust an online pharmacy
https://trusted-online-generic.com/?search=pitavastatin
Thank you for your wonderful job. Kind regards.
REPLY
Daniel 
JANUARY 16, 2020 AT 4:06 PM
HI Nathalie,
I like Dr. Richardson for his very nice work as well as taking that one step closer to the
clinical space. Nevertheless, in my view Pitavastatin is only one of the tools to be used.
Metformin would add extra value in my view, as discussed here
https://www.cancertreatmentsresearch.com/reduce-cholesterol-in-cancer-cells-to-fight-
cancer/
In the article above I did not addressed Metformin because I specifically wanted to have the
post addressing Statins and Mevalonate Pathway which is a relevant approach to fight
cancer.
Kind regards,
Daniel
REPLY
nathalie G 
JANUARY 16, 2020 AT 7:16 PM
Thank you ! I see your message just when I’m connecting to tell you that I have finally
seen your other article and understood your logic of separating the articles. Your
confirmation is welcome.
REPLY
kapil.agrawalkapil
Hi Daniel – For some reason, my previous comment has not shown up.
Just for continuation sake, the clarification on Pitavastatin dosage, frequency and concomitant use
with Lipodox and Cyclophosphamide Chemo, I have already emailed Dr Alan Richardson but I got his out
of office till Sep 23rd. As my Mother has her third Chemo shortly afterwards, it would be ideal to get
some directions sooner than that.
Many Thanks again,
Kapil
REPLY
Daniel 
Hi Kapil,
Your comment was in “spam” – I had to rescue it and approve it. Whenever this happens again
please let me know. Please see how I would start with Pitavastatin in the Source and Administration
section of this post. I would start with 2mg/day split in two (morning and evening), for two weeks
and switch off this for another two weeks. This should cover the time until Dr. Richardson is back
and can guide your oncologist towards higher doses, step by step.
Please also read this https://www.cancertreatmentsresearch.com/community/repurposed-drugs-

and-new-substances/fenbendazole-mebendazole-for-tnbc/#post-1157
Kind regards,
Daniel
REPLY
kapil.agrawalkapil
Hey Daniel – I cannot thank you enough for your detailed and comprehensive as well as such timely
responses.
My Mother is getting Lipodox along with a big dose of Cyclophosphamide every 3 weeks. She also gets
Zoldria (Zoledronic Acid which is a type of Bisphosphonate) with these two drugs.
We have started her on 2mg * 2 (morning and evening) on Pitavastatin from today. Would you know if it
is best taken with food or on empty stomach. Based on your discussion with Dr. Richardson, I hope he is
fine with Zoldria being given as the primary idea of Zoldria is to address the bone lesion.
Separately, Dr Richardson has just now responded to me. I will let my Mother’s Oncologist speak to him
directly. I will share the details as I get from him for everyone’s benefit.
REPLY
Daniel 
Great to hear Dr. Richardson will be in contact with your mom’s oncologist!
REPLY
Gokhan Can
DECEMBER 30, 2019 AT 9:58 PM
If the underlying cancer is driven by a microbe, statins may also help eradicate that.
Antibacterial activity of statins: a comparative study of Atorvastatin, Simvastatin, and Rosuvastatin
Majed Masadeh,corresponding author1 Nizar Mhaidat,1 Karem Alzoubi,1 Sayer Al-azzam,1 and Ziad
Alnasser2
Background
Statins have several effects beyond their well-known antihyperlipidemic activity, which include
immunomodulatory, antioxidative and anticoagulant effects. In this study, we have tested the possible
antimicrobial activity of statins against a range of standard bacterial strains and bacterial clinical
isolates.
Methods
Minimum inhibitory concentrations (MIC) values were evaluated and compared among three members
of the statins drug (atorvastatin, simvastatin, and rosuvastatin).
Results
It was revealed that statins are able to induce variable degrees of antibacterial activity with
atorvastatin, and simvastatin being the more potent than rosuvastatin. Methicillin-sensitive
staphylococcus aureus (MSSA), methicillin-resistant staphylococcus aureus (MRSA), vancomycin-
susceptible enterococci (VSE), vancomycin-resistant enterococcus (VRE), acinetobacter baumannii,
staphylococcus epidermidis, and enterobacter aerogenes, were more sensitive to both atorvastatin, and
simvastatin compared to rosuvastatin. On the other hand, escherichia coli, proteus mirabilis, and
enterobacter cloacae were more sensitive to atorvastatin compared to both simvastatin and
rosuvastatin. Furthermore, most clinical isolates were less sensitive to statins compared to their
corresponding standard strains.
Conclusion
Our findings might raise the possibility of a potentially important antibacterial class effect for statins
especially, atorvastatin and simvastatin.
REPLY
Daniel 
Perfect point! Actually statins have anti-viral action too.
While doing the research on statins I came across these activities of statins, and thought this is
amazing – yet again, another major category of anti-cancer drugs pointing towards cancer as a
parasitic/viral/bacteria/fungal triggered and driven disease. Too many arrows pointing towards the
same direction …
REPLY
Gokhan Can 
Yep, also the observation that metastatic colon cancer cells carry their bacteria with them!
Absent bacteria, cancers stops metastasizing.
https://www.dana-farber.org/newsroom/news-releases/2017/study-finds-colorectal-cancer-
cells-and-bacteria-to-be-fellow-travelers-during-metastasis/
Do you have any thoughts on RCC? I found out it carries epstein barr virus. (“Expression of
Epstein-Barr virus in renal cell carcinoma.” Oncol Rep. 2007 Jul;18(1):41-6). I’m not really sure
what would eradicate that, alongside with the cancer.
Many thanks. Super helpful website. Clearly a work of dedication.
REPLY
nathalie G
JANUARY 19, 2020 AT 11:48 AM
Hello, Daniel and everybody,
My oncologist was quite open-minded to write to Doctor Richardson who kindly reply ; Daniel, if you
consider that oncologists must write to Dr Richardson to have the following informations, please
remove this post. Anyway, these are just details that overlap with what you wrote.
As you said, it is necessary to have a high dose of drug for a short time, and then take a break before
resuming. Dr Richardson recommends 2 weeks of Pitavastatin with a diet. Start with normal doses and
explore higher doses (doses will be indicated in private communication with Dr. Richardson). Close
monitoring is absolutely necessary due to toxicity (on the muscles in particular). Then take a 2 weeks
break.
During the 2 weeks with Pitavastatin, as you noted, diet without geranylgeranium is important.
So, must avoid : Sunflower oil, corn oil, Dolmio pasta sauce.
Preferably avoid : Grape seed oil, groundnut oil, lettuce.
Only if necessary : rape seed oil, sesame oil, bread, cheese, butter, milk, pasta (not tinned), dsrawberry
jam, squash, tomato, potato, kiwi, passion fruit, cherry, gooseberry, pears, figs.
-I would like to have a list of foods with their GG contents, but it doesn’t seem to exist.
-Most importantly, I would like to have Pitavastin rather than Atoravastin. If Dr Richardson chose it,
there are reasons ; and as it is written at the top of this page : “a statin that seems to be the more
effective against cancer of all statins”. It can give give me a better chance while improving the data.
So, would anyone know in which country Pitavastatin is available ? Especially in Europa. Because I can
come from France and get it. At the same time, If manage to have a french prescription, will it be
accepted ? Thank you for any response.
REPLY
Daniel 
JANUARY 20, 2020 AT 1:15 AM
Dear Nathalie,
Thank you for sharing this info. In order to protect Dr. Richardson and patients, I removed the
discussion about the dose mentioned by Dr. Richardson to the oncologist as it is outside of the
normal dose and was private communication towards the oncologist. For anything that goes beyond
the approved dose, it is best that goes under the supervision of a medically trained person. So the
point remains valid – if the patient would like to explore higher doses, it is recommended to have his
oncologist contacting Dr. Riochardson to ask what are those doses.
Kind regards,
Daniel
REPLY
nathalie G 
JANUARY 20, 2020 AT 10:57 AM
Hello Daniel,
You’re absolutely right, it’s wiser.
Have a nice day.
REPLY
nathalie G
FEBRUARY 1, 2020 AT 12:04 AM
Finally, Pitavastatin is available in Switzerland with a prescription. Not only in Switzerland, but I had
it from Switzerland.
REPLY
Daniel 
Great to hear that Nathalie!
REPLY
nathalie G
Platelets, what else ? (!!!)
Hello Daniel, hello everybody,
Always the same problem : drop in platelets. I’ve seen that Prednisolone would improve platelets, vitamin K2 and papaya leaf tea. I’m a little bit
worry about papaya leaf tea because it has an antioxidant action and I chose oxidation. I don’t know about K2 (?). It was told me that it would
be a good idea with D3. Melatonin could work also, but the dosage in the link below seems to be antioxidant (nothing comparable to those of
the Riordan Clinic).
– > Please, any other idea ?
– A scientific question, because I don’t understand very well : is there a danger in wanting to increase platelets ? Increase cell division ? Is it
better to wait for Mother Nature to wake up ? (I don’t think so, but…)
https://www.google.com/search?client=safari&rls=en&q=prednisolone+increase+platelets&ie=UTF-8&oe=UTF-8
https://ouhsc.edu/platelets/TTP/bridget.html
https://www.researchgate.net/publication/286207894_Experimental_data_about_melatonin_effects_on_platelet_count_and_functional_activity
Thank you for any message, have a nice week-end !
REPLY
jshaw
Can anyone recommend a source of generic pitavastatin, such as a reputable online pharmacy?
REPLY
Daniel 
There are 3 online pharmacies listed that can be trusted (one i tried myself and others have been
recommended by other people here) https://www.cancertreatmentsresearch.com/suppliers/ I
checked the first one and they have Pitavastatin.
Kind regards,
Daniel
REPLY
jshaw 
I’ll check them out, thank you so much.
REPLY
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25/2/22, 18:33 Making Cholesterol-Lowering Statin Drugs More Effective Against Cancer - Cancer Treatments - from Research to Application

Cancer Treatments – from Research to Application

NEWS & OTHERS

POSTED ON JULY 21, 2019 BY DANIEL

Statin Drugs More Effective  Search …

This important information is related to the following:

First, here is a little background for those new to the subject:

Statins (e.g. atorvastatin, lovastatin, simvastatin, pravastatin, pitavastatin, rosuvastatin, mevastatin,

precursor for the biosynthesis of  johan on Colon and Colorectal

cholesterol production in cells. Cholesterol  Jcancom on Colon and Colorectal

gastric cancer (Ref.)  Pulse on Colon and Colorectal

RE: What to take/stop during

@corsaro1 I forgot to add your

Yes, it Works! Successful Case Report in Humans

mitochondria modulation (Ref.)

Side Effects and Toxicity

Also read this: Statin Safety and Associated Adverse Events

Source and Administration

New interferon/lovastatin treatment to battle cancer

An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer

OBJECTIVE: The statin family of cholesterol-lowering drugs has been shown to induce tumor-specific

METHODS: Deregulation of HMGCR expression in PCa was evaluated by immunohistochemistry. The

Statin Use and Reduced Cancer-Related Mortality

Statin-dependent modulation of mitochondrial metabolism in cancer cells is independent of

Statins, widely used to treat hypercholesterolemia, inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A

Statin drugs to reduce breast cancer recurrence and mortality

Curbing Lipids: Impacts ON Cancer and Viral Infection https://www.ncbi.nlm.nih.gov/pubmed/30717356

Statins enhance efficacy of venetoclax in blood cancers

inhibition suppressed protein geranylgeranylation, resulting in up-regulation of proapoptotic protein p53

Ovarian cancer: Statins might be effective with diet control

Statins could ease coughing in lung disease patients, study finds

Statins improve the anti-tumor effects of ACLY inhibition

Background Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for

Setting Stroke center at an academic tertiary care hospital.

Conclusions Even brief exposure to atorvastatin causes a marked decrease in blood

Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer

Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy

Feedback Regulation of Cholesterol Synthesis

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?

 CANCER TYPES, CHOLESTEROL MODULATION, OVARIAN CANCER, TREATMENT STRATEGIES

← A Silver Bullet to Kill Cancer Neurofibromatosis type 1 (NF1) →

34 thoughts on “Making Cholesterol-Lowering Statin

Dear Friends, thank you for your support.

Thank you Daniel.

Thanks for your help.

Hi Daniel – I must say this is a GEM of a post!

1. My Mother is currently on IV Chemo: Lipodox and Cyclophosphamide. Could Pitavastatin be added

2. What would be advisable dose and frequency to get anti-cancer benefits.

Thank you for the positive feedback.

An extension of this strategy is discussed here https://www.cancertreatmentsresearch.com/reduce-cholesterol-in-cancer-

https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ as it would increase Doxo absorption by

To my knowledge, it can be taken with or withouth food.

In my view the addition of Bisphosphonates is perfect since it inhibits an enzyme (FPPS)

Pitavastatin is difficult to get, maybe here if we can trust an online pharmacy

Thank you for your wonderful job. Kind regards.

Many Thanks again,

Please also read this https://www.cancertreatmentsresearch.com/community/repurposed-drugs-

Antibacterial activity of statins: a comparative study of Atorvastatin, Simvastatin, and Rosuvastatin

Perfect point! Actually statins have anti-viral action too.

what would eradicate that, alongside with the cancer.

Many thanks. Super helpful website. Clearly a work of dedication.

Hello, Daniel and everybody,

Preferably avoid : Grape seed oil, groundnut oil, lettuce.