4.6 Review

HER2 targeted therapy in colorectal cancer: New horizons

Journal

CANCER TREATMENT REVIEWS
Volume 105, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ctrv.2022.102363

Keywords

Colorectal cancer; Targeted therapy; Human epidermal growth factor receptor; HER2; Precision medicine; ctDNA

Categories

Funding

  1. National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust, United Kingdom
  2. Institute of Cancer Research, London, United Kingdom
  3. Cancer Research UK Clinical Research Training Fellowship

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This article provides an overview of the clinicopathological features of HER2 amplification and mutations in metastatic colorectal cancer (mCRC), and its role as a biomarker of anti-EGFR resistance. The review also discusses the preclinical, clinical, and translational studies investigating the use of HER2 targeted therapies and future research.
Despite recent advances in the treatment of metastatic colorectal cancer (mCRC), 5 years survival rates remain low. Chemotherapy remains as the mainstay of treatment with only few available targeted therapies. Human epidermal growth factor receptor 2 (HER2) amplification occurs in approximately 5% of metastatic colorectal cancer and it has been studied as a mechanism of resistance for anti-epidermal growth factor receptor (EGFR) therapy. Furthermore, several studies such as HERACLES-A, MyPathway and the DESTINY-CRCO1 trials have shown significant clinical benefit of HER2 blockade in patients with HER2 amplified mCRC. In this review, we provide an overview of the clinicopathological features of HER2 amplification and mutations in mCRC. In addition, we review HER2 as a biomarker of intrinsic and acquired anti-EGFR resistance as well as the preclinical, clinical and translational studies investigating the use of HER2 targeted therapies and future studies.

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