Both the tumor genome (e.g., in the case of gefitinib therapy) and the patient's germline genome (e.g., in the case of irinotecan therapy) can contribute to pharmacogenomic variation in response to antineoplastic drugs. The tumor genome plays a critical role in the response to gefitinib (Panel A), since the sensitivity of non–small-cell lung cancer to this drug is enhanced by activating mutations in the kinase domain of the gene encoding epidermal growth factor receptor (). Tumor encoding activating mutations within the kinase domain results in enhanced tumor sensitivity to gefitinib. The rate of toxic effects associated with irinotecan (diarrhea and myelosuppression) is increased in patients with seven TA dinucleotide repeats rather than the more common six repeats in the promoter region of encoding a UDP-glucuronosyltransferase in germline DNA, resulting in lower enzyme activity and a decreased rate of drug metabolism (Panel B).
David Kisor, PharmD
Chair, Department of Pharmaceutical Sciences
Director, Master of Science in Pharmacogenomics Program
What might pharmacogenomics mean for you
Genetics and Genomics for Patients and the Public covers everything from detailed information about genetic disorders, background on genetic and genomic science, the new science of pharmacogenomics, tools to create your own family health history and a list of online health resources.
Personalized medicine and pharmacogenomics - Mayo …
There has been a good deal of comment in the scientific literature and the popular press about the slow pace of the application of genomics to clinical medicine. We hope that we have provided some reassurance that advances resulting from the application of genomic science to drug therapy may be helpful in drug selection and administration and reduce the odds of adverse drug reactions. Challenges that are associated with the replication of study findings and the development of proof of the clinical significance of implicated variants underscore the importance of functional experiments to test for biologic plausibility and to extend our understanding of drug mechanisms. Finally, a blend of scientific, regulatory, and psychological factors must be addressed if pharmacogenomic tests are to become a routine part of clinical practice. The FDA-mandated incorporation of pharmacogenomic information in drug labeling will remain an important step in the acceptance of pharmacogenomics in clinical practice. Perhaps equally important will be the willingness of physicians to reexamine suboptimal pharmacologic management programs.
Pharmacogenomics Market Size, Share, Analysis – …
In recent years, the FDA has aggressively pursued drug-label modification when excess risk can be convincingly linked to a genetic marker. Several of the examples have been described here; many more are listed in the FDA's Table of Pharmacogenomic Biomarkers in Drug Labels (). Warnings that the FDA has issued about the prescription of clopidogrel and abacavir without testing of the relevant genotype are examples of the agency's increasingly activist stance.
Pharmacogenomics: Precision Medicine and Drug …
The use of genotyping to inform clinical decisions about drug use is not widely practiced. The slow pace of the clinical application of pharmacogenomics has many causes. Obviously, the most important issue is the need to establish clinical utility in order to support the value of genotyping. In the absence of such evidence, payers will be unlikely to provide reimbursement for routine use of pharmacogenetic testing, and tests will remain inaccessible to the majority of patients. There seems to be little consensus on the level or nature of data required to establish clinical utility.