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The Concept
The concept of Synthetic Lethality (SL) refers to the use of drugs for undruggable cancer cell treatment. It refers to a genetic principle in which a couple of genetic alterations involving deadly ones are not subject to SL that kills the intended target. There are two critical aspects that underpin the identified genetic principle. Firstly, the genes targeted with SL do not necessarily mutate in cancer (Bhattacharjee & Nandi, 2017). Hence, the interactions of these drugs in cancer treatment can potentially expand the number of targets. This concept is especially appropriate if the mutagen is undruggable. Secondly, the impact of drugs that have no clinical activity can be used in combination with a synthetically lethal second drug. These drugs always focus on the genes that mutate into cancer (Bhattacharjee & Nandi, 2017). However, mutations are associated with vulnerabilities that therapy can exploit, increasing these medicine substances effectiveness. This concept, therefore, tries to find a correction to abnormalities that occur along the DNA base. The essay aims to demonstrate that SL is an effective therapy that triggers two mutations in cancer cells that lead to cell death in the result.
The use of drugs for cancer treatment depends on the evidence that mutations that lead to cancer growth are associated with a particular weakness that can be addressed therapeutically. Modifications have been categorized into various cancer types based on cancer genome sequencing (Maria et al., 2018). These genetic transformations consist of the acquired-ability mutations in which the genes are translocated, amplified, or mutated, and loss-of-function mutations through the deletion of individual genes. Such changes as the deletion of DNA strands or replication present themselves together with the associated weak point that can be exploited to correct such abnormality. That is the essence of the therapy of colon and rectal cancer. It takes advantage of such weaknesses to bring normality to cell replication the drugs used for the treatment target specific proteins that will inactivate the mutation process.
Molecular Considerations in Synthetic Lethal Cancer Treatment
The killer of cancer cells targets a persons metabolism to restrain uncontrolled growth and cell proliferation through antimetabolites. These antimetabolite drugs inhibit nucleotides synthesis, therefore reprogramming the cancer cells to normal cell replication (Sinicrope, 2018). Certain metabolic features have been identified in the cancerous cells, including glycolysis and glucose intake. The tumor cells utilize certain enzymes which are currently targeted by the oncologist and have proven to be positive (Srivas et al., 2016). The enzymes include hexokinase, pyruvate kinase, lactase transporters, and glucose transporters (Sinicrope, 2018). Therefore, dysregulation of metabolism is very critical in countering the effects of tumor growth. These cells metabolize glycogen, and when the enzyme, glycogen phosphorylase, is exhausted by the use of drugs, the tumorigenesis stops.
Specific metabolites such as proline, serine, glutamine and glycine are also utilized to energize the tumorigenesis by providing hydrogen and carbon. Treatment substance that targets such metabolites also kills the cancer cells, such as applying the drug, then inhibiting glutaminase enzymes (Sinicrope, 2018). Such inhibitors act to improper alterations of the tumor with no effect on average cell growth. Inhibition effects have been used to treat various strains of cancer, including hepatocellular carcinoma, prostate cancer, melanoma, renal carcinoma, and hepatocellular carcinoma (Sinicrope, 2018). Lipid metabolism is also linked with carcinogenesis, and the inhibition of its breakdown significantly reduces the survival of cancer cells. Targeting metabolism pathways reduces tumor growth. However, these pathways are so complex that this therapys efficiency is reduced, hence the adoption of SL in cancer treatment.
Therapeutic Agents in Synthetic Lethality of Cancers
SL is applied to two genes, causing mutation in one of them and automatically killing the other. It is a developing concept in cancer treatment that promotes a drug that induces death in the malignant genes while causing no harm to the other gene (Weiser, 2018). Potentially, therapies involving SL have less toxicity to normal cells that have no specific reactivity to the therapeutic agents applied. The drugs used for SL have been designed with particular sensitivity to affect the cancerous cells exclusively. They can work alongside chemotherapy, but their complexity allows them to function even when chemo drugs have failed (Weiser, 2018). Similar to other medications, they spread throughout the body via the bloodstream reaching even those malignant cells that travel to other areas.
These therapeutic agents have different targets and are classified according to their intended goals. Some drugs help in developing blood vessels by inhibiting Vascular Endothelial Growth Factor (VEGF) (Sinicrope, 2018). The factors are proteins in nature and help cancer cells produce new blood vessels and facilitate the intake of nutrients that helps the tumor to survive. Such drugs prevent proteins from functioning and can be used to cure rectal and colon cancers. They are invested in a patients blood vessels and are considered to increase life span (Grasso et al., 2018). Some of these drugs are Bevacizumab (Avastin), Ziv-aflibercept (Zaltrap), and Ramucirumab (Cyramza).
Some medications target cells that experience BRAF gene modifications: specific genetic modification involved in relaying cell growth signals. These medications are based on oncogene that stimulates cell development as needed; however, their mutation leads to unabated cell proliferation (Sinicrope, 2018). Encorafenib (Braftovi) is used as an inhibitor against such gene alternations; It is combined with cetuximab to boost their effectiveness in reducing the spread of colorectal cancer. Regorafenib (Stivarga) is a growth inhibitor that targets the kinase enzyme. Kinase is a protein substance present on the cell surface, and it relays signals that direct cell maturity. These proteins are constrained by Regorafenib that prevents uncontrolled cell enlargement. The drug can also stop the production of new vessels in the cell, hence preventing tumor swelling.
Conclusion
Most of these drugs are associated with adverse health effects that can further deteriorate the patients condition. They cause extreme tiredness, diarrhea, headaches, low blood cell counts, and even increased blood pressure. There are also rare side effects that include severe bleeding, kidney problems, heart problems, and blood clots. They exhibit various side effects; however, most of those received via infusion cause allergic reactions. Therefore, it is necessary to address these adverse health impacts associated with these agents to ensure they are applied appropriately. However, these medications can control the increasing number of cancer cases and reduce the death toll globally.
References
Ashworth, A., & Lord, C. J. (2018). Synthetic lethal therapies for cancer: Whats next after PARP inhibitors. Nature Reviews Clinical Oncology, 15(9), 564.
Benjamin, D., Robay, D., Hindupur, S. K., Pohlmann, J., Colombi, M., El-Shemerly, M. Y., & Hall, M. N. (2018). Dual inhibition of the lactate transporters MCT1 and MCT4 is synthetic lethal with metformin due to NAD+ depletion in cancer cells. Cell Reports, 25(11), 3047-3058. Web.
Bhattacharjee, S., & Nandi, S. (2017). Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combined therapeutics. IUBMB Life, 69(12), 929-937.
Grasso, C. S., Giannakis, M., Wells, D. K., Hamada, T., Mu, X. J., Quist, M., Nowak, J. A., Nishihara, R., Qian, Z. R., Inamura, K., Morikawa, T., Nosho, K., Abril-Rodriguez, G., Connolly, C., Escuin-Ordinas, H., Geybels, N. S., Grady, W. M., Hsu, L., & Hu-Lieskovan, S. (2018). Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discovery, 8(6), 730-749.
Siegel, R. L., Miller, K. D., Fedewa, S. A., Ahnen, D. J., Meester, R. G., Barzi, A., & Jemal, A. (2017). Colorectal cancer statistics, 2017. CA: A Cancer Journal for Clinicians, 67(3), 177-193.
Siegel, R. L., Miller, K. D., & Jemal, A. (2020). Cancer statistics, 2020. CA: A Cancer Journal for Clinicians, 70(1), 7-30. Web.
Sinicrope, F. A. (2018). Lynch syndrome-associated colorectal cancer. New England Journal of Medicine, 379(8), 764-773.Â
Srivas, R., Shen, J. P., Yang, C. C., Sun, S. M., Li, J., Gross, A. M., Jensen, J., Licon, K., Bojorquez-Gomez, A., Klepper, K., Huang, J., Pekin, D., Xu, J. L., Yeerna, H., Sivaganesh, V., Kollenstart, L., van Attikum, H., Aza-Blanc, P., Sobol, R. W., & Ideker, T. (2016). A network of conserved synthetic lethal interactions for exploration of precision cancer therapy. Molecular Cell, 63(3), 514-525.Â
Thanikachalam, K., & Khan, G. (2019). Colorectal cancer and nutrition. Nutrients, 11(1), 164.Â
Weiser, M. R. (2018). AJCC 8th edition: Colorectal cancer. Annals of Surgical Oncology, 25(6), 1454-1455.
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