Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF

Bioorg Med Chem Lett. 2013 Jan 15;23(2):394-401. doi: 10.1016/j.bmcl.2012.11.037. Epub 2012 Nov 21.

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.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Humans
  • Melanoma / drug therapy*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics*

Substances

  • Enzyme Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf