Using Gene Therapy as a Treatment for Cancer - Developments and Future Prospects - Literature review Example

?Using Gene Therapy as a Treatment for Cancer - Developments and Future Prospects This paper explores the scope of gene therapy for cancer treatment in the context of current developments and future prospects. Cancer is the second potential cause of death in Western countries. Cancer mainly affects human organs including lung, prostate, and bone. Breast cancer is common in females. Although scientists have proposed a series of therapies that can improve patient outcomes, definitive cure for cancer has not been developed yet. Over the last decade, researchers gave more emphasis on gene therapy development as they believed that this treatment method would effectively contribute to cancer prevention. The process of gene therapy is mainly concerned with the modification or alteration of genetic material such as genes and DNA, which play a notable role in determining the characteristic traits of individuals. Different gene therapy methods mainly focus on three basic approaches and they are destruction of cancerous cells, prevention of the growth of cancerous cells, and improvement of normal cells’ ability to fight against the affected cells. In gene therapy, viruses are used to replace cancerous cells instead of inserting genes directly into the patient’s body. The U.S. Food and Drug Administration has banned the use of retroviruses since experiments showed that this virus may cause the development of other diseases like leukemia. By the end of 2010, more than 1060 gene therapy protocols have been suggested or practiced for various cancers; this figure constitutes over 64% of all gene therapy experiments in humans in the United States. Although, majority of such trials reported modest therapeutic responses, the clinical efficacy of such practices is still to be proven. The major disadvantage of gene therapy method is the possibility of infection of the healthy cells attributed to the viruses used for gene delivery. Introduction The history of gene therapy started during the beginning of the 1960’s. In the opinion of Bettelheim, Brown, Campbell &Farrell (2010, p. 721), gene therapy is a complicated medical procedure by which genes within an individual’s cells and biological tissues are altered, and removed in order to treat diseases. In other words, the gene therapy intends to correct a genetic mutation by the addition, alteration, or removal of specific genes. By the application of gene therapy, the restored cells get the proper instructions for building proteins and thereby the body mechanisms return to the normal state. In 1970, Stanfield Rogers, an American doctor at Oak Ridge National Laboratory, tried to apply gene therapy as a method to treat two sisters who had suffered from a genetic disorder called argininemia (‘History of gene therapy’ 2011). Although, Rogers’ effort was unsuccessful, it is considered as a milestone in the history of gene therapy development. By the end of 1977, scientists could successfully apply gene therapy techniques to deliver a gene into the cells of mammals (‘Gene therapy/ human genome project/ history of gene therapy/ future of gene therapy’ n.d). As Jain (2000, pp. 3-4) points out, the year 1989 witnessed tremendous improvements in gene therapy development when scientists began to research the scope of gene therapy in cancer treatment. A team of researchers including, Drs. Kenneth Culver, W. French Anderson, Michael Blaese, and Steven Rosenberg conducted a study to evaluate the safety and effectiveness of the gene therapy process in cancer patients. The research team “grew tumor infiltrating lymphocytes (TIL cells) from people with the deadly cancer malignant melanoma, and then they engineered a virus to put a DNA market into those cells” (‘Gene therapy’ n.d). This experiment assisted the researchers to conclude two things: TIL cells can be applied to treat cancer and the engineered virus can effectively and safely work in humans. (Baruch 2005) tells that in 1990, American doctor W. French Anderson conducted a detailed research on a four-year-old girl who had a genetic disorder called severe combined immunodeficiency, with intent to explore the scope of gene therapy in humans. As part of his study, Anderson genetically restructured the girl’s white body cells and restored them to her body. Eventually, it seemed that white blood cells could strengthen the girl’s immune system and therefore assist her to return back to normal life. (Wharam 1999) notes that the field of gene therapy attained another significant achievement in 2000 when a French researcher named Alain Fischer cured similar kind of immune system disorder in children. In his experiment, Fischer inserted a retrovirus (gene carrier) into the children’s blood stem cells and several months later, he identified that two of the children under observation developed a disease similar to leukemia (a type of cancer). As a response to this experiment result, US Food and Drug Administration (FDA) banned the use of retroviruses in the United States (‘Gene therapy legislation in the US’ 2011). Recently, in 2006, scientists at the National Institutes of Health in Bethesda developed a method to successfully treat metastatic melanoma using Killer T cells and they cured two patients with this disease (‘what is gene therapy?’ 2011).This success influenced the medical world to certify the gene therapy process as an effective method for cancer treatment. Although, researches in the field of gene therapy are progressing slowly, they still move forward. Development of gene therapy Malignant neoplasm or cancer can be simply defined as the uncontrolled growth of abnormal cells in the body. Cancer is a dreadful disease as it is very difficult to bring back the individual to normal life unless his disease has not diagnosed at its initial phases. According to official data Yilmaz, Yazihan, Tunca, Sevinc, Olcayto, Ozgui, and Tuncer (2009, pp.10-16) cancer constituted 13% of all human deaths worldwide in 2007. Researchers hold the view that the causes of cancer generally come under two groups; environmental causes and hereditary genetic causes. Primarily, cancer is an environmental disease although there is a five to ten percent chance for genetic cancer. Recent developments in gene therapy indicate that this technique can be effectively employed to mitigate the horrible impacts of cancer. Hence, the scientific world vehemently tries to attain more improvements in cancer gene therapy treatment. (Kolehmainen 2000) says that the Food and Drug Administration has not yet approved the sale of human gene therapy product because the process of gene therapy has not been very successful in clinical trials. According to (Cotrim & Baum 2011), the gene therapy sector faced a major setback in 1999 as a result of the death of Jesse Gelsinger, an 18-year-old boy, who was participating in a gene therapy experiment. Some of the most recent developments in gene therapy process have given a new life to this treatment system. In 2009, a group of researchers from the School of Pharmacy in London successfully developed nanotechnology + gene therapy as a response to torpedo cancer (‘Nano- treatment to torpedo cancer’, 2009). The most potential feature of this treatment method is that it leaves healthy cells unaffected. Hence, this gene therapy offers a hope to people with severe cancers where surgery would not be possible. The research leader Dr. Andreas Schatzlein said that “Gene therapy has a great potential to create safe and effective cancer treatments but getting the genes into cancer cells remains one of the big challenges in this area” (‘Nano- treatement to torpedo cancer’ 2009). A study conducted on mice by researchers from the University of Texas MD Anderson Cancer Center and the University of Texas Southwestern Medical Center reflected the scope that an effective ‘combination of two tumor suppressing genes delivered in lipid-based nanoparticles’ notably minimizes the chances of human lung cancer (‘Gene therapy’, 2011). The researchers still conduct experiments to identify the scope of this treatment method in humans. In 2006, researchers at National Cancer Institute effectively reengineered immune cells with intent to target and destroy cancer cells in patients with advanced metastatic melanoma (‘New method of gene therapy alters immune cells for treatment of advanced melanoma’ 2006). The researchers conducted the experiment on 17 advanced melanoma patients and they observed sustained regression of the disease because the genetically shaped patients’ own white blood cells could recognize and attack cancer cells. (Arya 2011) points out the groundbreaking international study, in which a group of researchers successfully applied gene therapy in two adult patients who had been suffering from a disease affecting myeloid cells. This experiment success has of a great significance in gene therapy development since myeloid disorders are common and they may include different bone marrow failure syndromes including acute myeloid leukemia. Likewise, scientists have developed a new gene therapy approach that effectively revamps defects in messenger RNA which are derived from defective genes. The developers strongly argue that this technique has the potential to heal some type of cancers. Additional information Retroviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses are some of the different types of viruses that are commonly used as gene therapy vectors (‘Working with viral vectors’ 2011). In addition to virus based gene delivery systems, several nonviral options have been developed for gene delivery. Among the other options, direct insertion of therapeutic DNA into target cells is the simplest method. However, this method has only limited application because it can be applied to only certain tissues and it needs comparatively large amounts of DNA. (Kaplan n.d) says that the formation of an artificial lipid sphere with an aqueous core is another nonviral method of gene delivery system(. Researchers also try to develop a 47th chromosome so as to introduce it into the target cells since such a chromosome can carry considerable amounts of genetic code (‘The contemporary psychiatry’ 2006). Scientists anticipate that body’s immune system cannot attack this artificial human chromosome because of its special construction and autonomy. At the same time, some others argue that it would be very difficult to deliver this type of a large molecule to a target cell’s nucleus. Similarly, it is observed that ranges of factors such as short-lived nature of gene therapy, immune response, problems with viral vectors, and multigene disorders impede gene therapy’s development as an effective treatment for genetic disease (‘Gene therapy’ 2011). In order to effectively identify the malfunctioning gene and replace it with a healthier portion, it is necessary to perform some genetic tests. In the words of (Lifton, Somlo, Giebisch & Seldin 2009), genetic testing raises many ethical as well as legal problems. Many people are of the opinion that genetic testing is the violation of privacy and they also argue that prenatal tests may lead to an increase in the number of abortions. Future of gene therapy Currently, a variety of gene therapy vector systems are being developed as a response to cancer. As a result of the complexity of some of the solid tumors like “angiogenesis, hypoxia, and stromal cell, tumor cell heterogeneity, and the emergence of de-differentiated stem cell”; every existing vector fails to offer a future scope (Good, Duan, Anne & Wei, n.d). It is clear that viral vectors cannot extensively use in future and this situation raises serious threats to the future of gene therapy since potential alternatives to viral vectors have yet to be developed. However, the clostridial spore based vector system has attained notable significance in the present days as it is not infectious and provides further scope for development. Likewise, there are a series of factors challenging the scope of gene therapy. In the opinion of (Scanlon 2004), scientists have not yet identified the key target genes for disease pathology and progression. He also opines that it is essential to discover the correct therapeutic gene that is capable of inhibiting the disease progression. Hence, it becomes a difficult task for the researchers to develop an effective system of gene therapy. If the existing gene therapy practices are continued without resolving related issues successfully, it will cause dreadful future impacts. Recently, a young man died as a result of the vector based gene therapy treatment. According to Dr. Anderson, “his death raised a red flag that gene therapy is not harmless”. He added that “the risk of a major immune, inflammatory response remains” (Wood 2011). Other similar incidents also raise ranges of questions regarding the potentiality of gene therapy in treating cancer. Two children in France developed syndromes like leukemia after a gene therapy because the gene they received had possessed cancer causing elements. This issue was not identifiable even for physicians who treated the children. Medical authorities still hesitate to give approval for gene therapy practice outside clinical trials because many expert scientists hold the view that it is highly experimental. However, Dr. Anderson and Curiel (Wood 2011) anticipate that gene therapy method can overcome the present challenges effectively and a commercial gene therapy treatment will be available within five years. However, gene therapy is identified to be the potential treatment for breast cancer that kills more than 40% affected women. In this situation, scientists predict that gene therapy has a prosperous future in the field of breast cancer treatment. If a patient’s natural immune system can be genetically altered with cancer-fighting genes, it will be possible to combat cancer since the altered cancer cells act as a cancer vaccine. Nowadays, scientists employ the gene therapy as a technique to stimulate patients’ immune response to cancer (‘How does gene therapy work?’ 2011). Under this method, proper genes are inserted into patients’ body with intent to produce a T-cell receptor (TCR) protein that has the ability to attach to the surface of the tumor cells. Progressively, the TCRs stimulate the white blood cells to destroy the tumor cells. This method can have a great influence on the effective prevention of cancer in future. Likewise, scientists are examining the scope of gene therapy to make the cancer cells more sensitive to cancer treatment methods such as chemotherapy and radiation therapy. Some studies investigate the potentiality of increasing the natural resistance capacity of the body to mitigate the side effects of higher anticancer drug doses. In another research approach, researchers inject a pro-drug into the patient’s body and it is activated in cancer cells by the insertion of “suicide genes” into the patient’s cancer cells. Scientists claim that this practice will eventually lead to the destruction of those cancer cells. Medical science also conducts ranges of studies to deploy gene therapy as an effective measure to prevent angiogenesis (the process of development of new blood vessels from existing cancer cells). In short, the future of gene therapy is uncertain and it also greatly depends on the ongoing research outcomes. Conclusion Evidently, gene therapy is a complex cancer treatment method and it is developing relatively in a slow pace. Some adverse incidents like treatment related deaths have greatly impeded the advancement of gene therapy. When the history of gene therapy treatment crossed a half century, this sector has no significant achievement to claim. Although, ranges of research results pointed out that gene therapy is a potential treatment method for cancer, the researchers failed to justify their argument empirically. As a result of the uncertain nature of cancer gene therapy treatment, the U.S. Food and Drug Administration (FDA) is not willing to commercialize this treatment method. In gene therapy approach, it seems that scientists focus more on diseases that are caused by single gene defects. However, the past experiences point that such a gene therapy system would not be much effective since it is very difficult to carry and deliver DNA to the correct site on the gene. Gene therapy development faces some ethical and legal challenges also since genetic tests like prenatal testing associated with gene therapy may lead to a series of social issues like abortion. 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