Pharmacogenetics in Cancer - Essay Example

Pharmacogenetics in Cancer Introduction Variations between people in the toxi along with efficacy of drug therapy are often linked with polymorphisms in genes encoding drug-metabolizing enzymes, drug targets, or transporters. In the recent past, the advances in pharmacogenetics have progressively unveiled the genetic basis of interindividual variations in response to drugs. A huge portion of these advances have been done in the field of cancer therapy (Weng, et al., 315). In other words, some of the most advanced applications of knowledge in pharmacogenetic is in the field of cancer therapeutics. Various problems have been realized during the cancer therapy using the conventional chemotherapy. This is because to attain reasonable efficacy, a considerable degree of toxicity is needed and hence severe side-effects. Most oncologists are faced with the major challenge of the variability of the treatment responses as well as narrow therapeutic index for the anticancer drugs. Therefore, there is no doubt that the developments in molecular biology and molecular genetics, and of the associated methods have had considerable effects on the comprehension of drug action. Therefore, drawing on a variety of sources the paper will discuss pharmacogenetics in cancer Discussion Cancer is a very unusual disease because it emanates from the accumulation of several gene mutations within the cell, thus disrupting normal cellular function as well as normal checks. Therefore, cancer cells have definite genetic profiles. As result, pharmacogenetics is helpful as a cancer therapeutic since is focuses on the genetic profiles and a person’s interaction with the drug. Pharmacogenetics can be described as the interaction between the drug and individual traits, and is very helpful in cancer therapeutics. Therefore, it is based on the clinical efficacy observations as well as tolerability profile of a drug in a person (Licinio and Wong 129). The most common challenge in cancer treatment is the related to the anticancer drugs. The pharmacogenetics can assist in the discovery, development, and individualization of the anticancer drugs. As cited by Yong, Innocenti and Ratain (35), the first step towards pharmacogenetics translation into clinical practice is the identification of genetic variations that predict for drug response. In the same way, pharmacogenetics also established that a drug may act differently in one individual than another taking a similar drug for the same condition. The genetic approach of pharmacogenetics is developing a valuable tool to come up with a tailored therapy in cancer treatment. The principles of pharmacogenetics in cancer: a single gene encodes a protein like a drug-metabolizing enzyme whose function may be relevant to various drugs; several variants within the same gene may lead to various functional effects that can result in the absence of the protein and increased or reduced activity; the same enzyme may have several functional affects on the breakdown of various drugs, for instance, it may prevent the drug’s activity by facilitating its removal through catalyzing the conversion of the pro-drug to its active metabolite; finally, co-morbidities, adherence, and co-medications can impact on the drug metabolism (Newman 40-41). Pharmacogenetics testing is now being utilized in the treatment of people with particular types of cancer. First is colorectal cancer. Irinotecan is a chemotherapy method that is often used for the treatment of colorectal cancer. In certain persons, the variations in the genetic composition results in a shortage of the UGT1A1 enzyme. The enzyme is responsible for the body’s metabolism of irinotecan. The increased levels of irinotecan in the body lead to reduced levels of UGT1A1 enzyme in the body. This results in acute to potentially life-threatening side effects, particularly if the drug is administered at higher dose levels. The physicians might utilize the UGT1A1 test to determine if the patients have genetic variation, which will permit them to prescribe a lower irinotecan dosage for those patients. In most cases, the lower dose is often as efficient; even though less toxic in those people whose bodies are programmed to use the less effective form of UGT1A1. Stoehlmacher (81) asserts that this shows how pharmacogenetics evaluates associations between genetic polymorphisms in the metabolic genes along with clinical endpoints, like response, toxicity, therapy, and survival. As discussed in UGT1IA1, this polymorphism is associated with an elevated toxicity with irinotecan. The other pharmacogenetic knowledge of substances usually given to patients with colorectal cancer, include oxaliplatin and flouropyremidines. Second, acute lymphoblastic leukemia (ALL) can also be treated using pharmacogenetics. Physicians often utilize pharmacogenomic testing for children with severe lymphoblastic leukemia. This has led to ALL being a lethal disease about 40 years ago to the current cure rates of about 80 percent. The exemplary progress is attributed to the optimization of existing treatment modalities in contrast to the discovery of new antileukemic agents (Cheok, Pottier and Kager 39-41). The genetic variants affecting antileukemic drug effects or leukemic cell biology have been evidenced, including for instance variants in folate-dependent enzymes, metabolizing enzymes, influx and efflux transporters, and drug apoptotic proteins. The genetic variations in an enzyme that is referred to as thiopurine methyltransferase (TPMT) are found in an estimated 10% of the children. The decreased activity of thiopurine methyltransferase causes polymorphism in the TPMT gene resulting in acute toxicity with mercaptopurine. The thiopurine methyltransferase is responsible for the metabolism of the chemotherapy that is utilized to treat acute lymphoblastic leukemia. In order to avoid deleterious side effects, those children with lower thiopurine methyltransferase levels are treated with lower doses of these drugs. In the same way, as cited by (Barnes 227), dosage reduction is prerequisite for patients with homozygous or heterogenous mutation in this gene. Third, the estrogen receptor as well as human epidermal growth factor receptor 2 (HER) represents the major pharmacogenetic targets for effective therapies in breast oncology. The advances in genomic approaches to clarify prognosis have refined the utilization of cytotoxic chemotherapy. However, most women still receive unnecessary as well as ineffective treatment. The pharmacogenetic factors that participate in the metabolism of these drugs, especially the effect of debrisoquine hydroylase (CYP2D6) polymorphisms in the metabolism of tamoxifen have started to change the clinical practice (Newman 45). Proceeding further, another application of pharmacogenetics is in the genetic targeting of Herceptin (trastuzumab). This is an anti-body based therapeutic utilized for the treatment of HER2 positive breast cancer. Hercpetin competitively binds to the HER2, thus blocking the growth factor binding along with targeting the cancerous cells for destructions by the own systems of the body. The non-cancerous cells are affected minimizing the toxicity. However, purists share the view that Herceptin does not represent true pharmacogenetics since they target the tumor cells genetic nature instead of the patient’s genotype. The other types of cancers, such as stomach, and pancreatic can be treated using fluorouracil (5-FU, Adrucil) as a pharmacogenetic intervention. The genetic variation in certain people makes them to have reduced levels of an enzyme called dihydropyremidine dehydrogenase (DPD). It has been evidenced that the polymorphisms in DPD gene is associated with fluorouracil-related toxicity. About 6% of 5-FU undergoes anabolism into cytotoxic nucleotides to prevent tumor activity, while over 90% undergoes catabolism into toxic metabolites that are expelled in the urines (Barnes 131). According to Yong, Innocenti and Ratain (37), dihydropyremidine dehydrogenase assists in the metabolism of fluorouracil. The health practitioner may utilize the pharmacogenetic testing to become aware of these variations in patients, allowing them to reduce the drug dosage in order to avoid serious side effects in these patients. There are various challenges that are associated with pharmacogenetic testing. It is costly and not extensively available, and also the insurance plans may not cover the costs of the available costs. However, the researchers are working to come up with more effective and cheap testing methods. Besides that, the federal laws have been passed which prohibits insurers and firms to separate according to their genetic information. This has resulted in some legal, ethical, and privacy issues that are yet to be resolved that may affect the continued development of pharmacogenetics. Conclusion Pharmacogenetics established persons predisposed to the high risk of toxicity from conventional cancer of chemotherapeutic agents. It has been used as a cancer therapeutic with regard to the manner in which various individuals are able to respond to a certain drug. In cancer therapeutics, pharmacogenetics is emerging as an alternate approach to managing chemotherapy to prevent under-treatment while avoiding over-treatment in addition to related toxicities. By determining the polymorphic genetic makeup of the host, the cancerous cells can be suppressed based on the genetic profiles. Works Cited Barnes, Linda. New Research on Pharmacogenetics. New York: Nova Publishers, 2007. Print. Cheok, H., et al. "Pharmacogenetics in acute lymphoblastic leukemia." 46.1 (2009): 39-51. Licinio, Julio and Ma-Li Wong. Pharmacogenomics: The Search for Individualized Therapies. New York: John Wiley & Sons, 2009. Print. Newman, William. Pharmacogenetics: Making cancer treatment safer and more effective. Manchester: Springer Science & Business Media, 2010. Print. Stoehlmacher, Jan. "Prediction of Efficacy and Side Effects of Chemotherapy in Colorectal Cancer," Recent Results in Cancer Research 176 (2007): 81-98. Weng, Liming, Zhang, Li, Peng, Yan, and Huang, Stephanie. "Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy," Pharmacogenomics 14.3 (2014): 315-324. Yong, W., F. Innocenti and M. Ratain. "The role of pharmacogenetics in cancer therapeutics," Br J Clin Pharmacol 62.1 (2006): 35-46. Read More