Targeting receptor tyrosine kinases in HER2-negative breast cancer

Curr Opin Oncol. 2013 Nov;25(6):594-601. doi: 10.1097/CCO.0000000000000021.

Abstract

Purpose of review: The targeting of receptor tyrosine kinases (RTKs) has been a major area for breast cancer therapy, exemplified by the targeting of HER2-amplified breast cancer.

Recent findings: We review the data on the activation of RTKs in HER2-negative breast cancer, and discuss the clinical translational challenge of identifying cancers that are reliant on a specific kinase for growth and survival. Substantial evidence suggests that subsets of breast cancer may be reliant on specific kinases, and that this could be exploited therapeutically. The heterogeneity of breast cancer, however, and the potential for adaptive switching between RTKs after inhibition of a single RTK, present challenges to targeting individual RTKs in the clinic

Summary: Targeting of RTKs in HER2-negative breast cancer presents a major therapeutic opportunity in breast cancer, although robust selection strategies will be required to identify cancers with activation of specific RTKs if this potential is to be realized.

Publication types

  • Review

MeSH terms

  • Anastrozole
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Clinical Trials, Phase II as Topic
  • Disease-Free Survival
  • Drug Administration Schedule
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics
  • Female
  • Gefitinib
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy*
  • Nitriles / therapeutic use
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptor Protein-Tyrosine Kinases / drug effects*
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-3 / drug effects
  • Receptor, ErbB-3 / genetics
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Treatment Outcome
  • Triazoles / therapeutic use
  • Up-Regulation

Substances

  • Nitriles
  • Protein Kinase Inhibitors
  • Quinazolines
  • Triazoles
  • Anastrozole
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Gefitinib