The pharmacogenomics of drug resistance to protein kinase inhibitors. (September 2016)

• Record Type: Journal Article
• Authors: Gillis, Nancy K.; McLeod, Howard L.
• Is Part Of: Drug resistance updates. Volume 28(2016)
• Page Start: 28
• Page End: 42
• Publication Date: 2016-09
• Subjects: Pharmacogenetics -- Pharmacogenomics -- Cancer -- Resistance -- Somatic mutations; Drug resistance in cancer cells -- Periodicals; Cancer -- Chemotherapy -- Periodicals; 616.994061
• DOI: 10.1016/j.drup.2016.06.008
• Languages: English
• ISSNs: 1368-7646

Abstract

Abstract: Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance.