Jai N Patel1, Katherine Mandock, Howard L McLeod. 1. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA; UNC Institute for Pharmacogenomics and Individualized Therapy, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Abstract
BACKGROUND: The number of pharmacogenetic assays available is continuously expanding as more molecularly targeted anticancer drugs are under clinical development. While the literature regarding drug-gene associations and therapeutic implications is often robust, reviews regarding clinical assay availability and profiling methodologies of commonly used cancer biomarkers are often lacking. OBJECTIVE: To concisely identify and describe cancer biomarkers and their respective pharmacogenetic assays currently available in clinical practice. DISCUSSION: Analysis of germ-line DNA mutations can often help to predict pharmacokinetic and pharmacodynamic responses, whereas somatic DNA mutations are particularly useful in predicting tumor response. Molecular profiling and pre-emptive identification of cancer biomarkers can help to predict disease prognosis as well as response to anticancer therapy. Dozens of pharmacogenetic assays, utilizing several common methodologies, are currently available in clinical practice. It is essential for clinicians to understand the molecular pathways for anticancer drugs, the therapeutic implications of mutations within these pathways, the clinical assay(s) available to test for pharmacogenetic differences, and the common profiling methodology employed. CONCLUSION: As research continues to unveil more drug-gene and disease-gene associations, it is critical that clinicians understand which pharmacogenetic assays are available to identify inter-individual differences that predict safety and efficacy of anticancer drugs as we move toward the concept of personalized medicine.
BACKGROUND: The number of pharmacogenetic assays available is continuously expanding as more molecularly targeted anticancer drugs are under clinical development. While the literature regarding drug-gene associations and therapeutic implications is often robust, reviews regarding clinical assay availability and profiling methodologies of commonly used cancer biomarkers are often lacking. OBJECTIVE: To concisely identify and describe cancer biomarkers and their respective pharmacogenetic assays currently available in clinical practice. DISCUSSION: Analysis of germ-line DNA mutations can often help to predict pharmacokinetic and pharmacodynamic responses, whereas somatic DNA mutations are particularly useful in predicting tumor response. Molecular profiling and pre-emptive identification of cancer biomarkers can help to predict disease prognosis as well as response to anticancer therapy. Dozens of pharmacogenetic assays, utilizing several common methodologies, are currently available in clinical practice. It is essential for clinicians to understand the molecular pathways for anticancer drugs, the therapeutic implications of mutations within these pathways, the clinical assay(s) available to test for pharmacogenetic differences, and the common profiling methodology employed. CONCLUSION: As research continues to unveil more drug-gene and disease-gene associations, it is critical that clinicians understand which pharmacogenetic assays are available to identify inter-individual differences that predict safety and efficacy of anticancer drugs as we move toward the concept of personalized medicine.
Authors: Federica Saletta; Carol Wadham; David S Ziegler; Glenn M Marshall; Michelle Haber; Geoffrey McCowage; Murray D Norris; Jennifer A Byrne Journal: BBA Clin Date: 2014-06-28