The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML. Specifically, we examine the role of genetic variants in drug metabolism genes, i.e. CYP3A family genes, and drug transporters, i.e. ABC and SLC family genes. Additionally, we focus on acquired somatic variations in BCR-ABL1, and the potential role played by additional downstream signaling pathways, in conferring resistance to targeted drugs in CML. This review highlights the importance of PGx of targeted therapeutics and its potential application to improving treatment decisions and patient outcomes.
Bibliographical noteFunding Information:
RSH received support from the Avon Foundation research grant, NIH/NIGMS grant K08GM089941, NIH/NCI grant R21 CA139278, NIH/NIGMS grant UO1GM61393, Circle of Service Foundation Early Career Investigator Award, University of Chicago Support Grant (#P30 CA14599), Breast Cancer SPORE Career Development Award (CA125183), the National Center for Advancing Translational Sciences of the NIH (UL1RR024999), University of Chicago CTSA core subsidy grant, and a Conquer Cancer Foundation of ASCO Translational Research Professorship Award In Memory of Merrill J. Egorin, MD (awarded to Dr. MJ Ratain).
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