Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer

Mol Ther. 2023 Jul 5;31(7):1874-1903. doi: 10.1016/j.ymthe.2023.03.019. Epub 2023 Mar 22.

Abstract

Antibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity of a monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules to targeted cancer cells, leading to an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after the approval and tremendous success of trastuzumab emtansine and trastuzumab deruxtecan, representing a turning point in both HER2-positive breast cancer treatment and ADC technology. Additionally and importantly, a total of 29 ADC candidates are now being investigated in different stages of clinical development for the treatment of HER2-positive breast cancer. The purpose of this review is to provide an insight into the ADC field in cancer treatment and present a comprehensive overview of ADCs approved or under clinical investigation for the treatment of HER2-positive breast cancer.

Keywords: ADCs; HER2; HER2-postive breast cancer; antibody-drug conjugates; human epidermal growth factor receptor 2; immunoconjugates; targeted therapy.

Publication types

  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Immunoconjugates* / therapeutic use
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use

Substances

  • Trastuzumab
  • Antineoplastic Agents
  • Ado-Trastuzumab Emtansine
  • Receptor, ErbB-2
  • Antibodies, Monoclonal
  • Immunoconjugates