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Treatment Advances in Medulloblastoma

Shane Spiers
shanespiers@mail.usf.edu
U07078824
Biomedical Sciences
Thesis Director: Dr. Mark Jaroszeski
Prospectus

The issue of medulloblastoma is currently being personified as the


poster child of pediatric neuro-oncology. It is the most common malignant
pediatric brain tumor (Huang 2015). Medulloblastoma is characterized by a
metabolically active mass of tissue in the brain that starves the brain of
nutrients and compresses the surrounding cells, potentially sending stimuli
to the surrounding cells and simulating death signals. This particular genre of
cancer spreads through the cerebrospinal fluid, categorizing it as an
immensely deadly disease. Apoptosis, the process by which cells are preprogrammed to kill themselves usually as a defense mechanism, has been
thoroughly studied and is already understood. Cancer cells sometimes elicit
apoptotic responses, resulting in deterioration of bodily tissue. At steadystate cell life, a group of cells can divide and die at the same rate and so you
will neither accumulate nor run out of cells. A tissue can acquire a set
number of mutations at which point that cell can now hide from the immune
system and change growth kinetics. Once you change the balance or cell
growth or death, you grow a tumor. Cancer starves the body and tissues and
once it metastasizes, it grows even larger.
The immune system attempts to distinguish between what are normal
body cells from a wide variety of external agents. T-cells found in the human
bodys immune system are continuously attempting to remove cancerous
cells through apoptotic cascades. PD1 is a programmable death receptor on
the surface of T-cells, and is currently one of the most studied topics in

Oncology. Many cancer cells secrete a PD1 ligand that binds to PD1 receptors
on T-cells causing them to be driven into apoptosis. Cancer-derived
antibodies are able to neutralize the PD1 ligand, which is no longer able to
bind to the PD1 receptor and the T-cells are still able to function. Ketruda
(pembrolizumab) is an anti-PD1 antibody that has been released by Merck &
Co. for stage 3 metastatic melanoma, the 3 rd deadliest cancer in the US. The
Hedgehog Pathway is a major regulator of fundamental processes in the
body such as coordinating cell growth and development, and is currently
being studied as a means of medulloblastoma treatment (Huang, 2015). We
can also see that the research being done into vascular endothelial growth
factors, which are directly involved in immunosuppression and angiogenesis
in tumor biology, prove as potential for new therapy (Johnson, 2007).
Cancer patients are ostensibly noticed getting smaller as prognosis
continues. Many are under the impression that this is due to the effect of
cancer eating away at the body, however in actuality it is due to starvation
of healthy regions of the body by the cancerous cells. This is a booming area
of research where biologics and genes are now being used to attack those
genes and cancers. If you could take a biopsy of a tumor and conduct a gene
assay on the sample, we can find mutations and design a gene, drug or
antibody. Chemotherapy has been a popular reaction to the discovery of
cancer in a body, but it is actually a means of supplying enough poison that
doesnt kill the entire body. The process by which chemotherapy operates
does not directly target anything, and many times it can result in the

development

of

cancerous

cells

through

ingestion

of

carcinogenic

compounds in the treatment. We can see that the modulation of our immune
system can be the perfect vehicle for destroying tumor cells (Bustamante
Alvarez, 2015). The problem is that we need to develop a technique to train
the immune system to carry out the appropriate response. Though gene
therapy at the cell-response level can potentially be used to treat cancer,
most pre-existing research on the subject has been derived from animal
research and clinical trials.
Cancer is notoriously known for inducing a change in a persons diet.
As such, it may not be farfetched to suggest dietary modifications and
alternative medicine as a means of curing the aforementioned disease.
Ketogenic, paleo, low-sugar and organic diets have been anecdotally known
to positively contribute to the treatment of certain types of cancer (Hao et al,
2015). This stems from the fact that cancer cells metabolize these materials
and induce the activity of the cancer. As mentioned previously, tumorigenic
cells starve the body of nutrients in order to thrive, so to determine a way in
which you can starve the body of the nutrients which the cancer cells need
while keeping the rest of the body of the patient fully functional can be a
potential solution (Kapelner & Vorsanger, 2015).
Combination therapies (multi-faceted treatments comprising the use of
chemotherapy, antibodies, radiation, modulation of the immune system and
gene therapy) are proposed to be the most effective means of treatment of
the disease. Etoposide plus radiation therapy followed by combination

chemotherapy has been one recently tested treatment in children with newly
diagnosed advanced medulloblastoma (Childrens Oncology Group, 2014).
Despite aggressive treatment involving surgery, chemotherapy, radiation
and other therapies, most patients suffer devastating side effects. Thus, the
development of new treatment strategies is urgently needed. The focus of
this study will be to compile past and current information and potentially
determine the best means by which medulloblastoma could be treated given
recent advances that have been made within the field of oncology.

Proposed Work Schedule

October 30th Submission of Prospectus


November 1st January 10th Data collection, biweekly meetings with Dr.
Jaroszeski
January 11th Submission of 1st draft to the Chair
February 12th Submission of 2nd draft to the Chair
March 25th Submission of completed manuscript to the Chair, schedule
defense presentation
April 8th Preparation for final defense
April 15th Final revisions and preparation of manuscript for formatting
review

Works Cited

Bustamante Alvarez, J. G., et al. "Advances in Immunotherapy for Treatment


of Lung Cancer." Cancer Biol Med 12.3 (2015): 209-22. Print.

Childrens Oncology Group; National Cancer Institute. Etoposide Plus


Radiation Therapy

Followed by Combination Chemotherapy in Treating

Children With Newly Diagnosed

Advanced

Medulloblastoma.

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library


(US).

2000-

[cited

October

20 th

2015].

of

Available

https://www.clinicaltrials.gov/ct2/show/NCT00003573

NLM

In:

Medicine
from:
Identifier:

NCT00003573.

Hao, G. W., et al. "Growth of Human Colon Cancer Cells in Nude Mice Is
Delayed by Ketogenic Diet with or without Omega-3 Fatty Acids and
Medium-Chain Triglycerides." Asian Pac J Cancer Prev 16.5 (2015):
2061-8. Print.

Huang, S. Y., and J. Y. Yang. "Targeting the Hedgehog Pathway in Pediatric


Medulloblastoma." Cancers (Basel) 7.4 (2015): 2110-23. Print.

Johnson,

B.

F.,

et

al.

"Vascular

Endothelial

Growth

Factor

and

Immunosuppression in Cancer: Current Knowledge and Potential for


New Therapy." Expert Opin Biol Ther7.4 (2007): 449-60. Print.

Kapelner, A., and M. Vorsanger. "Starvation of Cancer Via Induced


Ketogenesis and Severe Hypoglycemia." Med Hypotheses 84.3 (2015):
162-8. Print.

Word Count

Prospectus word count: 875 words