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

Salvatore Siena, A. Sartore-Bianchi, S. Marsoni, H. I. Hurwitz, S. J. McCall, F. Penault-Llorca, S. Srock, A. Bardelli, L. Trusolino

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)1108-1119
Number of pages12
JournalAnnals of Oncology
Volume29
Issue number5
DOIs
Publication statusPublished - May 1 2018

Keywords

  • Biomarker
  • Colorectal cancer
  • HER2
  • Targeted therapies

ASJC Scopus subject areas

  • Hematology
  • Oncology

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