Mechanisms of lapatinib resistance in HER2-driven breast cancer

Cancer Treat Rev. 2015 Dec;41(10):877-83. doi: 10.1016/j.ctrv.2015.08.001. Epub 2015 Aug 8.

Abstract

Targeted therapies have been approved for various malignancies but the acquisition of resistance remains a substantial challenge in the clinical management of advanced cancers. Twenty-five per cent of breast cancers overexpress ErbB2/HER2, which confers a more aggressive phenotype and is associated with a poor prognosis. HER2-targeting therapies (trastuzumab, pertuzumab, TDM1 and lapatinib) are available, but a significant fraction of HER2-positive breast cancers eventually relapse or progress. This suggests that acquired or intrinsic resistance enables escape from HER2 inhibition. This review focuses on mechanisms of intrinsic/acquired resistance to lapatinib identified in preclinical and clinical studies. A better understanding of these mechanisms could lead to novel predictive markers of lapatinib response and to novel therapeutic strategies for breast cancer patients.

Keywords: Breast cancer; ErbB2/HER2; Lapatinib; Resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Amplification
  • Humans
  • Lapatinib
  • Mutation
  • Phosphotransferases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Quinazolines / therapeutic use*
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Receptors, Estrogen
  • Lapatinib
  • Phosphotransferases
  • ERBB2 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2