Strategies to overcome trastuzumab resistance in HER2-overexpressing breast cancers: focus on new data from clinical trials

BMC Med. 2014 Aug 12;12:132. doi: 10.1186/s12916-014-0132-3.

Abstract

Breast cancers over-express the human epidermal growth factor receptor 2 (HER2) in about 15% of patients. This transmembrane tyrosine kinase receptor activates downstream signaling pathways and leads to proliferation of cancer cells. Trastuzumab, an anti-HER2 monoclonal antibody, improves outcome in women with early and metastatic breast cancer. Resistance to trastuzumab involves the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway, truncation of the Her2 receptor or lack of immune response. The last decade has seen major advances in strategies to overcome resistance to trastuzumab. This includes the development of antibody-drug conjugates, dual HER2 inhibition strategies, inhibition of PI3K/mTOR pathway and development of modulators of immune checkpoints.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Humans
  • Receptor, ErbB-2 / genetics
  • Trastuzumab

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab