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Prevalence, prognosis and predictive status of HER2 amplification in anti-EGFR-resistant metastatic colorectal cancer

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Abstract

Numerous inherent and acquired genetic alterations have been demonstrated with resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC) patients. Although the common oncogenic driver mutations identified include KRAS, NRAS, BRAF, and PI3K, recent studies report a vital role played by human epithelial growth factor receptor-2 (HER2) amplification in acquired resistance to anti-EGFR therapy. HER2 amplification has been associated with poor prognosis in many malignancies including breast and gastric cancer and is also a negative predictor of anti-EGFR therapy. Given the relevance of HER2 amplification in conferring an anti-EGFR resistance, this paper reviews the prevalence of HER2 amplification in mCRC while exploring the prognostic and predictive values of this biomarker. Further, we also discuss the results of the studies that explored the utilization of anti-HER2-targeted therapies in mCRC. HER2-directed therapies have the ability to change the treatment algorithm in clinically relevant small subset of patients with HER2-amplified mCRC.

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Acknowledgements

We would like to thank Dr. Anuradha Nalli and Dr. Amit Bhat from Indegene, Bangalore, for providing medical writing support and technical assistance in the preparation of this manuscript, as funded by Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany.

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  1. Department of Medical Oncology, Anhui, The First Affiliated Hospital of University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, 230001, People’s Republic of China

    G. Wang, Y. He, Y. Sun, W. Wang, X. Qian & Y. Pan

  2. Merck Serono Co. Ltd., Pudong District, Shanghai, People’s Republic of China

    X. Yu

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Wang, G., He, Y., Sun, Y. et al. Prevalence, prognosis and predictive status of HER2 amplification in anti-EGFR-resistant metastatic colorectal cancer. Clin Transl Oncol 22, 813–822 (2020). https://doi.org/10.1007/s12094-019-02213-9

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