Genetic Precision: Paths to Cancer Being Solved through Targeted Gene Therapy

Marcela Barros 

The City College of New York

Writing for the Sciences – ENG 21003

Instructor: Debra Williams

November 15, 2023

Abstract 

The proposed study by Gene Therapy is significant because it has the potential to transform cancer treatment by identifying genes linked to cancer and modifying their expression to slow the growth and spread of tumors. Many of the cancer treatments used today are not precise enough, harming healthy cells in the process and producing unfavorable side effects. This problem is addressed by Gene Thepray’s method, which focuses on the molecular details of cancer genesis. The limited effectiveness of current treatments and the urgent need for more specialized and customized therapeutic interventions highlight the necessity of this research. A significant deficiency in earlier research is the absence of a thorough investigation of the particular genetic modifications that can be used to trigger apoptosis or interrupt the malignant cell cycle. The concern raised by this study is whether it is possible to manipulate these altered genes to fight cancer more successfully and selectively, or if doing so will harm the patients in the long run by changing their genomes. Furthermore, it is imperative to investigate the wider ramifications of this study, including possible uses in different forms of cancer and the long-term impacts on patient outcomes. To ensure the safety and efficacy of these genetic interventions across a range of patient populations, it might be possible to translate them into useful clinical therapies. This is something that could be looked into in a study proposal. To close this gap, the present research aims to discover the altered genes linked to cancer as well as to clarify how purposeful modifications to these genes may act as a focused and successful tactic against the growth of tumors. I hypothesize that If Gene Therapy successfully focuses and changes specific cancer-related genes then it should lead to helping reduce tumor growth and progression because the mutated genes could cause apoptosis or interfere with the cancerous cell cycle.

Introduction 

What is gene therapy? In the branch of biotechnology known as “gene therapy,” disease can be prevented or treated by introducing, modifying, or replacing genetic material within a person’s cells. Gene therapy’s main objective is to treat genetic problems by either fixing or making up for faulty genes. This strategy may offer long-term fixes, if not outright cures, for several hereditary illnesses. (FDA, 2018) Experts in the field of cancer gene therapy express optimism as well as caution. Numerous scientists emphasize the remarkable possibilities of gene therapy as a focused and customized method of treating different types of cancer. They place special emphasis on the capacity to add or change genes in a way that will boost the immune system’s defenses against cancer cells or selectively target and destroy harmful cells. Excitement has been stoked by encouraging outcomes from early-stage clinical trials, especially in hematological malignancies such as specific kinds of lymphoma and leukemia. Experts do, however, also recognize the complexity of cancer biology and the difficulties in obtaining long-lasting and consistent responses across a range of cancer types. There are worries expressed over the possibility of unexpected outcomes, the necessity for long-term safety evaluations, and the possible off-target impacts of gene editing technology. To completely comprehend the effectiveness, safety profile, and wider applicability of gene therapy in the intricate field of cancer treatment, ongoing research and clinical studies are essential. As gene therapy is still a new form of modern medicine it’s a very controversial topic many experts depict that there are many benefits and side effects as it is still being experimented with as “ they are still new approaches to treatment and may have risks. Potential risks could include certain types of cancer, allergic reactions, or damage to organs or tissues if an injection is involved.” (National institute of health,2022) Since the immune system may perceive the viral vector as an outside invader, using viral vectors to transfer therapeutic genes may cause immunological reactions in the body. This identification may cause inflammation, which in turn may lead to the altered cells’ demise. The use of genome editing techniques like CRISPR-Cas9 carries the danger of unforeseen genome modifications. When an editing tool alters genes other than the intended target, this is known as an off-target effect, and it can have unanticipated and sometimes dangerous results. It is yet unclear how gene therapy will affect people in the long run. Throughout a person’s lifetime, the effects of gene editing or the persistent expression of newly added genes may have unanticipated implications that demand more research. (Mayo Clinic, 2017)Many Experts think this is very dangerous if done too early but with time this can save thousands of lives.

Background 

It has long been known that angiogenesis and tumor progression are intricately related and that aberrant angiogenesis is a major mediator in the development of cancer. This article called “Tumor angiogenesis and anti-angiogenic gene therapy for Cancer” investigates the intricate process of angiogenesis, specifically the formation of tumors, and considers gene therapy as a possible treatment option for cancer. The article provides a thorough review of tumor angiogenesis, highlighting the vital function that it plays in promoting the development and spread of tumors. The issue of anti-angiogenic gene therapy becomes more pertinent in light of the theory that gene therapy can restrict tumor growth by targeting particular cancer-related genes. The concepts of gene augmentation and gene blockade are discussed, showing how the angiogenic switch may be broken and tumor vascularization eventually impeded by the introduction of anti-angiogenic genes or the suppression of pro-angiogenic genes. According to Folkman’s 1971 concept, angiogenesis must occur before tumors grow larger than a specific size, and this paper supports the idea that blocking angiogenesis could be a useful treatment approach. The discovery of many regulators, both pro- and anti-angiogenic, offers a biological foundation for gene therapy treatments. The potential of modifying particular genes to halt tumor progression is highlighted by the discussion of gene therapy approaches for cancer, including pro-apoptotic, suicide, and anti-angiogenic gene therapies. The article also discusses the difficulties associated with gene therapy, highlighting the significance of a reliable, secure, and targeted delivery method. Although gene therapy provides accurate molecular interventions, the relevant genes must be found and delivered to the appropriate area for these therapies to be successful. This supports the theory by highlighting the necessity of using two criteria to choose the proper genes and make sure they are delivered precisely to treat cancer. The article notes that although gene therapy has great potential, there are still obstacles to overcome, including immunogenicity, the possibility of off-target effects, and technical limitations in creating the best delivery methods. This admission challenges the theory by highlighting the fact that overcoming these obstacles is necessary for gene therapy to be successful. The limits of viral vectors—such as their toxicity and immunogenicity—are emphasized, indicating that more research is necessary to determine how best to employ them.

GBMs present significant obstacles in the field of oncology because of their aggressiveness and resistance to standard treatments. With a median lifespan of only eight months and a 5-year survival rate of less than 7%, the current standard treatments, which involve radiation therapy, chemotherapy, and neurosurgery, have limited success. Given this, gene therapy appears to be a viable option for creating cutting-edge therapeutic approaches. The use of baculoviral vectors (BVs) as possible substitutes for adenoviral vectors (AdVs) in gene therapy for glioblastoma multiforme (GBM) is examined in this article, “Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer.”The study presents baculoviruses (BVs) as a different kind of vector for neuro-oncology. In contrast to AdVs, BVs do not induce pre-existing human immunity, which may lead to more stable and long-lasting transgene expression, particularly in regions with favorable immune responses like the brain. Moreover, BVs are a desirable choice for gene therapy due to their high cloning capacity and ease of manufacture. My hypothesis suggests that tumor growth and progression may be inhibited if gene therapy is successful, especially if cancer-related genes are modified specifically. BVs offer a potential remedy in the context of GBM, where the immune system’s quick removal of vectors makes persistent gene expression difficult. The possibility of stable and persistent transgenic expression in the brain is increased in the absence of pre-existing immunity to BVs, which may improve the therapeutic effect on tumor cells. The use of BVs in preclinical assessments for delivering therapeutic transgenes for the treatment of brain cancer is also included in the text. The investigation of BV-mediated transgenic expression in both normal and cancerous astrocytes indicates that the vectors may be useful in addressing genes linked to cancer while reducing negative effects on normal cells. Although BVs are portrayed in the study as a prospective substitute, it is important to recognize that their effectiveness in clinical settings has not yet been established. While the absence of pre-existing immunity has benefits, there are also worries regarding the possibility of unexpected consequences and unchecked vector spread. The paper also mentions that although BVs transduce tumor cells effectively in vitro, their application as gene therapy vectors has not been tested in clinical trials. This calls into doubt the safety and viability of BVs when used on human subjects. To sum up, the article offers insightful information about the possibility of using baculoviral vectors as a gene therapy method for GBM. It is consistent with the theory that gene therapy may affect tumor growth if it is successful in bringing about specific alterations. To prove the safety and effectiveness of BVs in treating glioblastomas, more investigation and clinical validation are necessary, as the discussion makes clear. Investigating various vectors becomes essential as gene therapy advances to identify the best methods for enhancing patient outcomes in the difficult terrain of GBM treatment.

Methods 

Gene therapy presents a unique and focused method to address the intricate mechanisms behind tumor development and progression, which makes it a highly promising treatment option for cancer. The article “Advances in the Techniques and Methodologies of Cancer Gene Therapy” highlights the various strategies and vectors employed in gene therapy, emphasizing their potential to alter gene expression and correct genetic defects associated with cancer. This is consistent with the theory that, by causing apoptosis or disrupting the malignant cell cycle, gene therapy that effectively targets particular cancer-related genes may reduce the growth and progression of tumors. The necessity of secure and efficient gene delivery systems is highlighted by the selection of viral vectors, including retroviral, lentiviral, adenoviral, and adeno-associated viral vectors. The article explains how these vectors can change the expression of genes by introducing foreign nucleic acids into target cells. The capacity of these vectors to mediate stable, long-term gene expression is critical in the context of cancer therapy, supporting the theory that persistent alterations in cancer-related genes can influence tumor progression. The study also explores non-viral vectors and highlights their potential for in vitro gene therapy, including liposomes, cationic polymers, and nanoparticles. These vectors have the potential to carry a larger genetic load and offer higher safety levels. Although the article points out their present shortcomings in vivo settings, developments in these non-viral vectors may help gene therapy succeed in slowing the growth and spread of tumors. The article’s emphasis on cancer suppressor gene therapy reinforces the hypothesis’s linkage. The study highlights the possibility of gene therapy to regulate the balance between cell proliferation and death by examining tactics incorporating well-known tumor suppressor genes such as PTEN, P16, RB, and P53. The different approaches that have been explored, such as preserving the stability of wild-type p53 and introducing tumor suppressor genes, are directly related to the theory since they demonstrate how gene therapy might cause cancer cells to undergo apoptosis. Suicide gene therapy is discussed in detail in this section, along with how suicide genes can be introduced into tumor cells to use gene therapy to eradicate them. An important topic covered in the article is the bystander effect, which occurs when non-transduced cells are destroyed together with transduced cells. This method fits the concept by implying that gene therapy can cause apoptosis in the surrounding tumor microenvironment in addition to the targeted cancer cells. The article concludes by thoroughly examining the numerous aspects of gene therapy for the treatment of cancer, emphasizing the possibility of targeted modifications in genes linked to cancer to slow the growth and spread of tumors. Even though gene therapy has a lot of potential for identifying and changing particular genes linked to cancer, it’s important to be aware of any potential drawbacks and difficulties in refuting the theory. The complexity of the genetic landscape in cancer is one factor to take into account since various genes and pathways contribute to the development of tumors. Furthermore, the efficacy of gene therapy may differ based on the particular kind of cancer, and a comprehensive strategy that goes beyond targeting individual genes may be necessary for a successful reduction in tumor development and progression due to the complex interplay between multiple genetic components. The techniques and vectors that have been reviewed, coupled with their implications for inducing apoptosis and interfering with the malignant cell cycle, offer a strong basis for the theory that gene therapy can be an effective weapon in the fight against cancer.

My theory that gene therapy can slow the growth and spread of tumors by focusing on particular genes linked to cancer is well supported by the article “Gene Therapy for Cancer Treatment: Past, Present, and Future”. The article’s main focus is on the recently developed topic of cancer gene therapy, which includes a variety of therapeutic approaches that alter cells genetically to prevent or treat cancer. The main objective of the three broad categories covered in this article—gene transfer, oncolytic virotherapy, and immunotherapy—is to alter cancer-related genes to produce therapeutic effects. To strengthen the immune system’s ability to recognize and eliminate cancer cells, the article addresses the use of gene therapy to produce recombinant cancer vaccines. These vaccines are heading into clinical trials after showing potential in preclinical models through the alteration of autologous or allogeneic cells. The objective is to teach the patient’s immune system to identify cancerous cells and trigger an immunological response that lasts. Virolytic Oncolysis The article presents oncolytic vectors, and viruses with genetic engineering aimed at specifically targeting and eliminating cancer cells. Oncolytic treatments, such as adenovirus and herpes simplex virus type I, have shown promise in animal models and are currently undergoing human clinical studies. Oncolytic virotherapy targets cancer cells specifically, with little effect on healthy tissues thanks to its selective nature. Gene Transmission The introduction of foreign genes into cancer cells or surrounding tissue is known as gene transfer or insertion, and it is examined in this article as a potential therapeutic approach. Rexin-G, injectable gene therapy for pancreatic cancer, and TNFerade, which distributes the tumor necrosis factor-α (TNF-α) gene, are two examples. The variety of gene transfer methods that can be used to stop the proliferation of cancer cells is highlighted in the article. These choices include suicide genes and antiangiogenesis genes. The data in the article supports your theory by demonstrating how gene therapy treatments can alter genes linked to cancer, trigger apoptosis, and disrupt the cycle of malignant cells. There is hope that gene therapy may be a key factor in slowing the growth and spread of tumors, given the effectiveness of these treatments in preclinical models and ongoing clinical trials. The article’s conclusion bolsters the idea that developments in gene therapy have great potential for creating focused, efficacious therapies that target particular genetic defects linked to cancer and, in the end, slow the growth and spread of tumors. While the article supports my claims it also goes against it by countering that Certain people might hold to religious beliefs that stress the value of human life and contend that genetic modification—even in the interest of healing—interferes with the divinely instituted natural order. Modifying the genetic composition of living things may raise ethical questions in some religious contexts because it might be seen as interfering with the divine plan or taking on a role that belongs only to a higher power. As such, gene therapy talks may spark moral controversy in religious circles regarding the propriety of tampering with the genetic code and possibly altering the normal course of life, including the development of illnesses such as cancer. When examining the wider ramifications of gene therapy, it is imperative to recognize and tackle these ethical issues, particularly in light of differing religious viewpoints.

In conclusion, conducting a thorough study on the possible effectiveness of gene therapy that targets particular cancer-related genes has enormous potential to change the course of cancer treatment. If effective, this novel strategy may represent a ground-breaking intervention providing a tailored and targeted means of halting the growth and spread of tumors. We expect a large reduction in tumor burden by focusing on faulty genes and using gene therapy to trigger apoptosis or interrupt the malignant cell cycle. The expected results of this study include not only a deeper comprehension of the complex molecular pathways that underlie cancer but also the creation of new therapeutic approaches that can completely transform the way that cancer is treated. The main advantages of this suggested research ultimately lie in its ability to make a significant contribution to the area of oncology, opening the door to more customized and effective therapies that could lead to better patient outcomes and a resurgence of hope in the fight against cancer.

(Sources)

Li, T., Kang, G., Wang, T., & Huang, H. (2018). Tumor angiogenesis and anti-angiogenic gene therapy for cancer. Oncology Letters, 16(1), 687–702. https://doi-org.ccny-proxy1.libr.ccny.cuny.edu/10.3892/ol.2018.8733

Garcia Fallit, M., Pidre, M. L., Asad, A. S., Peña Agudelo, J. A., Vera, M. B., Nicola Candia, A. J., Sagripanti, S. B., Pérez Kuper, M., Amorós Morales, L. C., Marchesini, A., Gonzalez, N., Caruso, C. M., Romanowski, V., Seilicovich, A., Videla-Richardson, G. A., Zanetti, F. A., & Candolfi, M. (2023). Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer. Viruses (1999-4915), 15(3), 608. https://doi-org.ccny-proxy1.libr.ccny.cuny.edu/10.3390/v15030608

Sun, W. (2019, January 26). Advances in the Techniques and Methodologies of Cancer Gene Therapy. Weiming Sun – Discovery Medicine. https://www.discoverymedicine.com/Weiming-Sun/2019/01/advances-in-the-techniques-and-methodologies-of-cancer-gene-therapy/

Cross, D., & Burmester, J. K. (2006, September 1). Gene Therapy for Cancer Treatment: Past, Present and Future. Clinical Medicine & Research; Marshfield Clinic. https://doi.org/10.3121/cmr.4.3.218

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Benefits and Risks | NHLBI, NIH. (2022, March 24). NHLBI, NIH. https://www.nhlbi.nih.gov/health/genetic-therapies/benefits-risks

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