Cancer Chemotherapy Essay

Cancer Chemotherapy and Personalized Medicine Cancer is a leading cause of mortality worldwide. It is known to promote the harboring of accumulated genetic alterations in normal host cells, which then promote cancerous growth. Cancer chemotherapy attempts to eradicate or functionally disable tumor cells by the use of synthetic and/or natural compounds while preserving normal cells. Chemotherapeutic agents can eliminate tumor cells by direct cytotoxicity, activating host immune response, inhibiting the proliferation processes of tumor cells and inducing apoptosis. They are characterized by significant interindividual variations in pharmacokinetics (i.e. clearance and half-life) and pharmacodynamics (i.e. therapeutic responses and drug toxicities). Such variability primarily is due to multiple genetic factors arising from both tumor and noncancerous cells that lead to alterations in drug metabolism and transport, and/or drug targets (e.g. receptors or signaling transduction proteins). Chemotherapeutic agents typically have a narrow margin of safety, in that the ratio of the dose associated with antitumor efficacy and the dose associated with toxicity is small. These drugs are usually prescribed at a maximum tolerated dose (MTD) in order to achieve maximum cancer cell death; as such toxicity often is unavoidable, since there are frequently only subtle differences in the genome of cancer and normal host cells. The molecular basis of many pharmacogenetic polymorphisms has now been elucidated, and genetic defects have been found to occur in both coding and noncoding regions that disrupt protein function or abundance. In most cases a handful of mutations account for a large proportion of the population defects. The most common genot... ... middle of paper ... ... development of genetic tools and genotyping of tumor and patient prior to initiating treatment, antitumor efficacy may be increased with a substantial reduction in toxicity. Owing to the fact that many polymorphisms are likely to affect the outcomes of anticancer drug therapy, as well as other elements of supportive care, clinical trials must include enough patients to insure statistically significant results 75. Because most cancers are not considered 'cured' until a patient is cancer-free for 5 years from the time of diagnosis, even the best-planned pharmacogenetic clinical studies will take multiple years to yield useful information. As the investment in conducting well-planned clinical trials could easily exceed the investment required for genotyping, the public would benefit from incorporation of pharmacogenetic objectives into all cancer clinical trials.