Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer

Int J Mol Sci. 2016 Dec 14;17(12):2095. doi: 10.3390/ijms17122095.

Abstract

Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2) positive breast cancer (HER2+ BC) is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of breast cancer is HER2+ BC with significantly high expression level of HER2 protein compared to other subtypes. Therefore, HER2 is an important biomarker and an ideal target for developing therapeutic strategies for the treatment HER2+ BC. In this review, HER2 structure and physiological and pathological roles in HER2+ BC are discussed. Two diagnostic tests, immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH), for evaluating HER2 expression levels are briefly introduced. The current mainstay targeted therapies for HER2+ BC include monoclonal antibodies, small molecule tyrosine kinase inhibitors, antibody-drug conjugates (ADC) and other emerging anti-HER2 agents. In clinical practice, combination therapies are commonly adopted in order to achieve synergistic drug response. This review will help to better understand the molecular mechanism of HER2+ BC and further facilitate the development of more effective therapeutic strategies against HER2+ BC.

Keywords: HER2 positive breast cancer; antibody–drug conjugates; diagnostic tests; molecular mechanism; monoclonal antibodies; small molecular inhibitors; translational therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / therapy*
  • Female
  • Humans
  • Models, Biological
  • Molecular Targeted Therapy
  • Receptor, ErbB-2 / metabolism*
  • Translational Research, Biomedical*

Substances

  • Antineoplastic Agents
  • Receptor, ErbB-2