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Kaylin's Research Paper

Created By: Alberto Lopez
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Amazing.

Introduction 

Do you know someone who suffers from cancer? Chances are that you do. Cancer is a deadly disease that claims the lives of many each and every day. It is a leading cause of death worldwide and spreads pain and grief throughout communities. As the problem continues, many scientists are trying to find a cure to stop this vicious disease. Many different methods have been studied, researched, and experimented with. Although not all scientists agree, I believe that oncolytic virotherapy could contain the properties to make it the next revolutionary treatment that is able to effectively and efficiently cure cancer. 


Findings 

Cancer is a very significant and dangerous disease. It affects many people in today’s society. In fact, one of every four individuals' cause of death is cited as cancer (Siegel 2013, 1). There are over one hundred different types of cancer (Anonymous 2010, 3). Cancer occurs when damaged cells inside of the body begin to divide erroneously. This division causes lumps or masses, called tumors, to appear (Anonymous 2010, 1). These tumors begin to wreak havoc with the body. They can grow incredibly large, interfere with vital systems within the body, and release hormones that conflict with normal body functions (Acs 2013, 1). When cancer cells successfully invade the body and begins to spread to other parts of the body, metastasis is said to have occurred. (Anonymous 2010, 2). Some forms of cancer, such as leukemia, do not result in the formation of tumors. It is no surprise that cancer has a high death rate once if it is not diagnosed quickly. If the disease cannot be caught quickly and treated, an individual is likely to face debilitating symptoms, including death (Acs 2013, 2). The impact of cancer is undeniable. In 2013 alone, there will be 1,660,290 new cases of cancer and over 550,000 deaths resulting from this deadly disease (Siegel 2013, 2) (Acs 2013, 3 & 4). While there is not yet a complete cure for cancer, many scientists are out in the field working hard to find a solution. 

One form of biotechnological engineering that has gained a lot of attraction in recent years is oncolytic virotherapy treatment. Many scientists today believe that oncolytic viruses may contain the answer to ending cancer (Vile, Ando, et al. 2002, 1). Although this technique has been acknowledged and researched since the 1950’s, the lack of adequate resources and technology did not allow it to progress further (Li, Tong, et al. 2012, 6). However, the rapid growth of today’s society and its ingenuity has resulted in the reemergence and success of oncolytic virotherapy (Vile, Ando, et al. 2002, 3). Oncolytic virotherapy is the process by which certain viruses are introduced into the body. Viruses present an ideal way to attack cancer from the inside. These viruses selectively infect and break down cancer cells while leaving normal cells unharmed (Thompson 2013, 2). This targeted treatment makes it easier to kill tumor cells and lessen the impact of cancer on the body by eliminating cancerous cells (Paddock 2013, 3). Scientists believe that engineering oncolytic viruses to act as a biological weapon against cancer might be able to suppress or eliminate the disease completely. Although there are still many obstacles to get through, this new cancer treatment is starting to become more widely recognized as its unlimited potential continues to be tapped in to and developed further (Timmer 2013, 6). The promising results indicate that a solution for cancer may soon be found. 

In oncolytic virotherapy, scientists alter the genetic makeup of viruses in order to optimize their chances of destroying, eliminating, and combating cancer (Thompson 2013, 2), (Timmer 2013, 2). These viruses are specifically made for this purpose and serve no other function. The process of oncolytic virotherapy is very complex. Viruses are engineered in many different ways and forms, each with their own use (Li, Tong, et al. 2012, 1). The most commonly used virus in this method of treatment is the adenovirus (Fikes 2013, 4). This virus is responsible for causing the common cold and has been intensively explored. It is particularly appealing because biologists understand its biological impact after years of curing colds and have abundantly used the virus in molecular biology and other research (Nettelback, Curiel 2008, 1). Adenoviruses also carry favorable, distinct traits. For example, the genes that they carry into a cell work for a short period of time and then break down, making them viable candidates for genetic selectivity that do not permanently damage the body. Viruses can be applied through various means. Methods of applications include intramural delivery, viral vectors, and intravenous injections (Ferguson 2012, 1). Two main strategies are used during virotherapy in order to reproduce viruses and kill cancerous cells and tumors. The first strategy, called transductional targeting, involves scientists attempting to engineer viruses to selectively infect and destroy cells that have turned cancerous (Nettelback, Curiel 2008, 3). This method is the most commonly used. The second approach occurs when a small part of DNA, known as a tumor specific promoter, is placed on the genes of the virus. The promoter activates and permits the gene to function only in cancer cells. The virus can enter normal cells, but the promoter will not activate within them, disallowing them to reproduce or kill healthy cells. However, once in the cancer cells, the promoter activates and lets the virus make millions of copies of itself, bursting the cancer cells and spreading to other cancerous cells in the process (Nettelback, Curiel 2008, 4). 

Oncolytic irotherapy is very advantageous in many different ways. Some of the benefits of this method are that it is safe, can affect many types of cancer, and advances the medical field further than ever before (Nettelback, Curiel 2008, 6). Another reason that this method is favorable is because it is more efficient than traditional cancer eradication techniques, such as radiation and chemotherapy (Taber, Cheung 2010, 5). Oncolytic virotherapy kills a lower amount of healthy cells within the body, making it less damaging to important parts of the body such as bone marrow (Paddock 2013, 5). It can also affect a very broad spectrum of cancer types, making it a diverse and viable option. This method is very efficient at finding and eliminating cancer cells in the body without risking extra damage to other healthy cells that are not a threat (Taber, Cheung 2010, 6). The range at which oncolytic virotherapy is effective is large. One administration of a dose into an individual’s body can kill a large number of cancer cells and also provide access to tumors within the body that are in hard to reach places (Fikes 2013, 2). Lastly, the symptoms of oncolytic viruses are relatively tame in comparison to how much they help an individual. Within most clinical trials, patients given high dosage levels of oncolytic viruses only suffered flu-like symptoms lasting from twenty four to fourty eight hours (Paddock 2013, 5)(Li, Tong 2012, 5). 


Although its potential is evident, using virotherapy to treat cancer also presents some disadvantages. When patients are given multiple doses of virus therapy, the immune system begins to send out antibodies and white blood cells that start to recognize the virus. As a result, subsequent doses end up being less effective because the immune system will immediately bind and deactivate the virus (Vile, Ando, et. al 2002, 5). One of the major concerns with this form of treatment is that it's long term effects are still relatively unknown. In 1999, an 18 year old died after receiving an infusing of virotherapy. His body shut down after an overwhelming immune reaction to the large dose of viruses he had been given (Nettelback, Curiel 2008, 2). Since virotherapy is relatively new and expanding, scientists are still working on making viruses safer, but it is still too soon for scientists to determine if there are any significant factors that could damage a patient using this form of therapy. Also, creating these new viruses and altering their genes presents the danger of creating serious mutations or dangerous new diseases altogether (Taber, Cheung 2010, 6). However, these risks are always present in any type of anti-cancer therapy. In order to cure a dangerous and deadly disease, researchers must be able to take risks within reasonable boundaries. 



There have been many successful clinical trials of oncolytic viruses as cancer treatment. Many companies involved in oncolytic virotherapy have made significant progress and great strides in the field (Anonymous 2010, 4). In clinical trials, different phases are tested. Phase 1 tests are designed to make sure that the drugs are safe for patients receiving them. Phase 2 and 3 trials are performed in order to determine the correct dosage levels and how much power it takes to produce an effect. After these phases, the treatment gets circulated and, if they are approved, eventually get put on the market (Nettelback, Curiel 2008, 5). 

Onyx-015, developed by Onyx Therapeutics, is a unique virus that has the potential to treat cancer effectively. Onyx-015 was created by genetically modifying an adenovirus and was extensively tested in trials to see if it could treat cancer (Thompson 2013, 3). This virus has the ability to detect the absence of p53, a specific protein with the body that all cancer cells lack (Timmer 2013, 3). As a result of this adaptation, the virus ignores normal cells and can only attack cancerous cells that lack the p53 protein. Onxy-015 is currently capable of targeting and destroying half of all major cancer types but is less effective against others (Vile, Ando, et al. 2002, 5). This virus has been tested in clinical trials extensively, with data suggesting that it is safe and selective for cancer (Li, Tong, et al. 2012, 3). However, the drug is ineffective alone and needs to be coupled with chemotherapy for optimal use, somewhat limiting its long term effectiveness (Ferguson 2012, 2). Research and funding has mostly ceased until the virus can show further potency. 


Another virus that has undergone clinical trials in an attempt to defeat cancer is OncoVex, developed by BioVex (Thompson 2013, 5). Clinically, this drug can function by itself and does not need to be paired with other treatments, such as radiation or chemotherapy. This virus originates from a modified cold sore that replicates inside solid tumors, causing cancer cells to die (Nettelback, Curiel 2008, 7). Also, the drug prompts the immune system to flag and subsequently eliminate cancer cells (Nettelback, Curiel 2008, 8). One of the downsides of this virus is that it can only be directly injected into tumors, making it unable to reach and treat any metastatic tumors that may have spread throughout an individual’s body. This virus has currently completed Phase 2 trials and is expected to enter the next test of trials soon (Li, Tong 2012, 7). If successful, research will continue and the Food and Drug administration will consider the drug for approval. 


However, one of the most effective clinical trial to date utilizes a genetically engineered vaccinia virus, known as JX-594, as its test subject (Ferguson 2012, 3). This virus is already widely used in vaccinations and has a reputation of being safe, making it a viable candidate to test against cancer. This particular virus was modified in order to make it more cancer selective. The virus also increases immune system stimulation (Li, Tong 2012, 4). This virus works in two different ways. First, the virus recognizes and targets cancerous cells and reproduces inside of them, resulting in their death. Secondly, the virus helps induce immune responses towards cancerous cells and makes the body attack cancer cells (Fikes 2013, 5). The results, reviewed by analysts, determined that all dosage levels resulted in anti-tumor activity (Li, Tong 2012, 5). Further research showed that the 69% of patients displayed some form of resistance to cancer. The average life span of cancer patients utilizing this drug was also increased. The JX-594 virus is currently in phase 3 clinical testing and its data looks very encouraging (Thompson 2013, 4). 





Conclusion 

Although oncolytic virotherapy has not yet been proven to completely cure the deadly disease of cancer, the success that it has experienced and impact it has made on the medical field has been undeniable. This form of virotherapy shows a promising future as more and more companies and biologists alike continue to invest their time into finding a cure for cancer. Although great strides have been made in this area, there is still plenty of room for more development. More viruses are continuing to be genetically modified and virotherapeutic strategies continue to be investigated. It is expected that the collective efforts of the biological researchers and pharmaceutical companies will continue to contribute to the development of effective and safe viruses for cancer therapy. Scientists have done the previously unthinkable. Viruses, things that were once a cause of sickness, are now being used to wage warfare against one of the top killers in the world. Medicine is being revolutionized once again as the goals of science are being tested upon and expanded further than ever previously thought. In order to move forward and continue with this promising research, we must continue to probe, dissect, and understand the potential that viruses carry.
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