Pharmacogenetics and Pharmacogenomics of Targeted Therapeutics in Chronic Myeloid Leukemia

Abstract

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.