Ginn 1 Lauren Ginn Instructor: Malcolm Campbell English 1102 27 March 2014 The Tumornator: Is Antiangiogenic Therapy the

new Cure for Cancer? A 35 year old woman goes in for her annual checkup just like she does every year; shes feeling healthy and living her busy life as a wife, teacher, and mother of two beautiful children. A week after her checkup, she receives a call from the doctors office telling her she needs to come in right away theres urgent news. Thinking little of it, she goes in to get the results; she cant stay too long because her son needs to be picked up from soccer practice in an hour and food needs to be on the table by six for the family. Little did she know, her life would be changed forever in that doctors office with the utterance of five simple, yet catastrophic words. The doctor walks in with a look on his face that screams devastation; the woman, now worried for her health and future, begs the doctor to tell her what he has to say. He can barely look at her when the life-shattering phrase Im sorry, you have cancer comes from his mouth. This horrific scenario is played out daily all over the world, affecting every life in some way, shape, or form. The silent killer has taken hold of more than 13,000,000 people in the United States the number increasing more and more each day. On average, as many as 500,000 people die each year from some type cancer in the United States, and 1,000,000 or more people are diagnosed with cancer each year in the United States (SEER). Because of these alarming statistics, cancer research has become more prevalent in todays society. In recent years, the National Cancer Institute has received a budget of over four billion dollar for cancer research alone, with the budget increasing by millions of dollars each year (Cancer). As time

Ginn 2 has passed, People have become more desperate than ever for a cure to this daunting disease and will not stop the fight until the battle is won and cancer is no longer a threat to the lives of millions of people. Within the last two decades, a new type of cancer treatment, antiangiogenic therapy, has been researched and developed as a possible cure or combat to cancer. According to William Li, M.D., the founder and president of Angiogenesis Foundation, Angiogenesis is the growth of new capillary blood vessels in the body. This process is essential for life it helps to heal wounds, build tissue, and transport needed nutrients throughout the body. When angiogenesis is out of balance, it causes multiple health problems. According to Li, Abnormal blood vessel growth, either excessive or insufficient, is now recognized as a common denominator underlying many deadly and debilitating conditions, including cancer.(Li et. al) In order for cancer to grow and spread, it must have some type of blood and nutrient provider and a transport mechanism this is the part angiogenesis plays in cancer growth. According to the National Cancer Institute, a research facility dedicated solely to the development of cures for cancer, angiogenesis [] is necessary for cancerous tumors to keep growing and spreading (Lifetime). In order for angiogenesis to occur, the VEGF growth factor, a pathway that is used in order to initiate a certain function in the body to take place, must be signaled (Takahashi). Once angiogenesis has been established and blood vessels have been developed to feed the cancer, it is able to not only receive the nutrients it needs to grow, but also has the ability to travel through the blood vessels to other parts of the body. This stage of cancer, known as metastasis, is very lethal. It allows cancerous cells to spread from one central location to multiple locations via the blood vessels and creates a cancer that is much harder to fight.

Ginn 3 Once cancer has reached this stage, the changes of death are increased by an average of 50%. (What is?). In order to combat metastasis and the growth of cancer in general, William Li and his team of oncologists have hypothesized that if cancer is attacked from the main source of growth and the VGEF factor is blocked there will be no possible potential for the cancer to become advanced; this will lead to the shrinking and disappearance of the cancerous tumor (Li et. al). In simpler terms, the main purpose of antiangiogenic therapy is to starve out cancer by cutting off its blood and nutrient supply. When antiangiogenic therapy was first introduced to the public in the late 1990s, it created a sense of hope that cancer might be able to be cured. According to the CNN News report in 1999 about this subject, [] researchers generated excitement by announcing a novel way of treating cancer -- by cutting off the flow of blood to tumors in mice. However, they were not able to supply the results as fast as the studies of the medicines were demanded. One of the first antiangiogenic drugs to be tested, thalidomide, took up to 6 years to be fully tested and brought to people with cancer as a possible treatment. This is because of the after effects that could possibly be seen with the use of these medicines. This drug (was) best known for causing tragic birth defects, according to CNN News journalist Dan Rutz, when doctors in some countries prescribed if for nausea in early pregnancy (Rutz). The fact that antiangiogenic drugs stop angiogenesis in multiple places besides just the designated area of treatment is a risk factor in many people because it could potentially cut off the blood supply. For this reason, antiangiogenic drugs available on the market are, to this day, few and far between. Some research since this time has proven antiangiogenic therapy to be an asset for future battles against cancer. William Li, one of the major advocates for antiangiogenic therapy and the

Ginn 4 importance of controlling angiogenesis, has conducted several experiments and found that antiangiogenic drugs can, in fact, stop the growth of cancerous tumors. In his presentation with TEDTalks, Li presents his data to give the general public an overview of the recent findings in antiangiogenic research. While presenting his data, he shows the difference between the use of antiangiogenic drugs as opposed to using radiation or chemotherapy. According to Li, When [] breast cancer was treated with Avastin, the cancerous tumor decreased by as much as 80%. Li also concluded from his tests and research that severe cancer in humans, dogs, dolphins, and horses can be treated with a mixture of antiangiogenic drugs and prolong the person or animals lifespan by as much at 7 years (Li). This research from the Angiogenesis Foundation is used in support of the antiangiogenic chapter of cancer research and sheds light on the great advances being made in cancer research in general. Along with this research, Li has also found that the diet a person uses can be helpful in fighting cancer. According to his research, 35% of all cancers are related to a persons diet. If a person is to surround themselves with antiangiogenic foods and drinks, such as pomegranate, pineapple, wine, and green tea, they will lower their chances of cancer and keep angiogenesis in check before it becomes a problem in a persons life. All of these findings by William Li and his team have been used as the fundamentals for many of the studies that have been conducted within the last two decades. Aside from Lis research, other oncologists have found positive results while working with antiangiogenic drugs and using them as part of their cancer treatments. In a recent study performed by the Tongji Medical College in China, the antiangiogenic drug Bevacizumab was used on a total of 103 patients with cancer, with the results showing that the antiangiogenic drug had the potential in most cases to prolong a patients life by as much as one year or more (Su et. al). With this information, people are more likely to gravitate towards this kind of treatment in

Ginn 5 order to prolong their life and, in some cases, save themselves from death. In another study performed by the University of Colorado, Dorte Neilson and his team used 150 women with breast cancer and treated them different antiangiogenic drugs, including Bevacizumab. Through their study, they found that with a mixture of different antiangiogenic drugs breast cancer can be healed. (Neilson et. al). With all of this information, it is easy to assume that antiangiogenic treatments will become part of the cancer regimen for future patients and their fight with the silent killer. In addition, some studies have also proven antiangiogenic therapy to not be enough to fight cancers on its own. In a recent study performed by the Department of Oncology at the University of Copenhagen, mice with cancerous tumors were treated with a mixture of different antiangiogenic medicines. The results from a six week experiment showed almost 70 percent of their mice did not show progress in fighting off the cancer. From their study, they concluded that treating cancer strictly with a mixture of different antiangiogenic medicines is not enough to fight cancer and keep it at bay. Some type of chemotherapy or radiation must also be used in order to really combat cancer (Anderson). Such a finding sets back the thoughts about antiangiogenic therapy and brings more skepticism to the table about its benefits if it truly has any at all. Other experiments, such as ones from performed by S.M. Sagar, an MD and research specialist in holistic health, tested multiple types of natural antiangiogenic sources, including shark cartilage, and found that they had little to no effect on the cancer. From his data, he and his team concluded that antiangiogenic therapy did not help to cure cancer in any patient with holistic healing process (processing with only natural remedies and no harmful or dangerous chemicals). (Sagar). This provides the awareness that antiangiogenic therapy is not enough to combat cancer on its own, in some cases, and must be paired with one of the other known

Ginn 6 treatments for cancer, such as radiation. This information that has been added to the knowledge of antiangiogenic therapy will help to further research on this topic. Along with this information, some oncologists have found some severe side effects that occur because of the use of antiangiogenic drugs. According to a study by David Cunningham, an oncologist from London who has spent his life researching cancer, side effects such as hypertension (high blood pressure), proteinuria (excessive serum proteins in urine),thrombosis (blood clots inside blood vessels), internal bleeding, impaired wound healing, and gastrointestinal perforation (a hole that develops through the entire esophagus, stomach, small intestine, large bowel, rectum, or gallbladder) occurred while a patient was using antiangiogenic drugs. However, it was found that the most common side effect was hypertension, which occurred in approximately 20% of the 105 patients that were tested. The most dangerous side effect, gastrointestinal perforation, only occurred in about 1.5% of the 105 patients (Cunningham). This gives antiangiogenic therapy some validation because it proves to not be as detrimental as some other forms of treatment that affect the entire body in harmful ways. This data collected by Cunningham is challenged, however, by the research performed by other oncologists and researchers in recent years. In a study conducted by the Department of Cell Therapy and Hematology from San Bortolo Hospital in Vicenza, Italy, it was found that the use of antiangiogenic drugs actually caused severe bleeding and clogging of the vascular endothelial growth factor (VEGF) (Elice). While the growth factor needs to be blocked in order to prohibit angiogenesis from occurring, clogging or bleeding at the location of the VEGF growth factor can be detrimental to the overall health of the body; it can cause severe internal bleeding, blood clots, and death. This finding sets back the use of antiangiogenic drugs because adding health problems

Ginn 7 on top of cancer will only put a patients life further at risk of death a risk most oncologists are unwilling to take. Along with this finding, some studies have found that blocking the VEGF factor only suppresses the cancer for so long at some point the cancer will start growing again and will reach the metastatic stage. Gabriele Bergers and Douglas Hanahan, both cancer researchers from the University of California, studied the possible resistance to antiangiogenic drugs. The scientists cultured cancerous cells in a petri dish for many months until it became a tumor; after this, an antiangiogenic injection was introduced to the tumor and the progression or regression of the tumor was followed. From their research, they found that over a prolonged period of time a cancerous tumor being treated with antiangiogenic drugs would start growing and spreading again. From this, they studied what could cause this growth of the tumor; they concluded from their research that two main reasons are the source for this growth: evasive resistance, an adaptation to circumvent the specific angiogenic blockade; and intrinsic or pre-existing indifference (Bergers). In simpler terms, the cancer either adapts in order to overcome the barrier created by antiangiogenic drugs, or they are naturally resistant to the drugs and they have no effect on them. These results, which completely contradict what had been found in earlier tests over the years, created skepticism and allowed for further research into the topic. Other scientists have also established the same results as Bergers and Hanahan concluded in their 2008 research. In a recent study conducted by F. Shojaei of the Oncology Research Unit in the United States, different patients with colon, breast, ovarian, ect. cancer were treated with a mixture of antiangiogenic drugs. The results showed that many of his patients that were treated with a mix of antiangiogenic drugs eventually showed a resistance to this cancer and the tumor eventually started growing again (Shonjaei). From this research, scientists are still trying to

Ginn 8 piece together the puzzle and discover what causes a certain cancer to be resistant to antiangiogenic drugs and possible mechanisms to overcome this resistance to make the drugs more effective. Overall, antiangiogenic therapy is still in the middle of being tested and the future for the treatment is very unclear. While it has been proven to have some benefits, the complications, risks, and inconsistency of its results makes antiangiogenic therapy a treatment that needs to be researched developed. With this development, the amount of potential problems and setbacks with the treatment can be decreased or possibly eliminated. As research continues to be done, there is no limit to what can be uncovered about this type of cancer treatment and cancer in general. Only time will tell the overall effect antiangiogenic therapy will have on cancer and the changes it will bring to treating the silent killer.

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Works Cited Bergers, Gabriele and Douglas Hanahan. Modes of resistance to anti-angiogenic therapy. Nature. Nature. August 2008. Web. 24 March 2014. Cancer Research Funding. National Cancer Institute. National Cancer Institute. 23 July 2013. Web. 14 March 2014. Cunningham, David, MD. "Antiangiogenic Therapy in Colorectal Cancer: Managing Side Effects." Medscape Oncology. Np. Web. 25 Mar. 2014. Elice, F., and F. Rodeghiero. Side Effects of Antiangiogenic Drugs. Np. April 2012. Web. 30 January 2014. Li, William, M.D. "Can We Eat to Starve Cancer? TEDTalks. May 2010. Web. 30 January 2014. Li, William, M.D., Michelle Hutnik D.Sc., Roderick Smith M.S., and Vincent Li M.D.. Understanding Angiogenesis. Angiogenesis Foundation. Angiogenesis Foundation. 27April 2012. Web. 8 February 2014. Lifetime Risk of Developing or Dying From Cancer. American Cancer Society. American Cancer Society. 5 Aug. 2013. Web. 12 Mar. 2014. Neilson, Dorte, Michael Anderson, Jon Anderson, and Claus Kamby. Antiangiogenic Therapy for Breast Cancer. Breast Cancer Research. N.p. 2010. Web. 1 February 2014. Rutz, Dan. A year after raising hopes, tumor-starving drugs still in lab. CNN News. CNN. 7 May 1999. Web. 21 March 2014.

Ginn 10 Sagar, S. M., MD, D. Yance, MH, and R. K. Wong, MD. "Natural Health Products That Inhibit Angiogenesis: A Potential Source for Investigational New Agents to Treat Cancer." Current Oncology. N.p. Feb. 2006. Web. 2 Mar. 2014. SEER Stat Fact Sheet: All Cancer Sites. National Cancer Institute. National Cancer Institute Web. 12 Mar. 2014. Shojaei, F. Anti-angiogenesis Therapy in Cancer: Current Challenges and Future Perspectives. National Library of Medicine. N.p. 28 July 2012. Web. 6 February 2014. Su, Yuan, Wei-Bing Yang, Li, Shi Li, and Zhi-Jian Ye. Effect of Angiogenesis Inhibitor Bevacizumab on Survival in Patients with Cancer: A Meta-Analysis of the Published Literature. Plos One. Np. Web. 2 February 2014. Takahashi, S. Vascular Endothelial Growth Factor (VEGF), VEGF Receptors and their Inhibitors for Antiangiogenic Tumor Therapy. National Library of Medicine. Np. Web. 29 January 2014. Understanding Cancer Series. National Institute of Health. N.p. 28 January 2005. Web. 29 January 2014. What is Metastic Cancer? American Cancer Society. American Cancer Soceity. 17 July 2012. Web. 8 February 2014.