title: Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF.
abstract: In the past decade, several kinase inhibitors have been approved based on their clinical benefit for cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. This review will focus on the cases of acquired resistance to EGFR and ALK inhibitors for non-small cell lung cancer patients and BRAF inhibitors for melanoma patients. I will overview the main causes of acquired resistance, and explore the chemical scaffolds as well as combination of drugs, used to tackle these major causes of resistance.
authors.affiliation: Vertex Pharmaceuticals Incorporated, 130 Waverly St., Cambridge, MA 02139, USA. simon_giroux@vrtx.com
authors.forename: Simon
authors.initials: S
authors.lastname: Giroux
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf