Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer

Ann Oncol. 2018 May 1;29(5):1108-1119. doi: 10.1093/annonc/mdy100.

Abstract

Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. Using functional and genomic analyses of patient-derived xenografts, we previously showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC) tumors is driven by amplification or mutation of HER2. This paper reviews the role of HER2 amplification as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target in CRC, considering the specifics of HER2 testing in this tumor type. While the role of HER2 as a biomarker for prognosis in CRC remains uncertain, its relevance as a therapeutic target has been established. Indeed, independent studies documented substantial clinical benefit in patients treated with biomarker-driven HER2-targeted therapies, with an impact on response rates and duration of response that compared favorably with immunotherapy and other examples of precision oncology. HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of metastatic CRC patients.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Chemotherapy, Adjuvant / methods
  • Clinical Trials as Topic
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Disease-Free Survival
  • Gene Amplification
  • Genetic Testing
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Precision Medicine / methods
  • Prognosis
  • Progression-Free Survival
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2