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.

Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer / S. Siena, A. Sartore Bianchi, S. Marsoni, H.I. Hurwitz, S.J. Mccall, F. Penault-Llorca, S. Srock, A. Bardelli, L. Trusolino. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 29:5(2018 May 01), pp. 1108-1119. [10.1093/annonc/mdy100]

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

S. Siena;A. Sartore Bianchi;
2018

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.
biomarker; colorectal cancer; HER2; targeted therapies
Settore MED/06 - Oncologia Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/576031
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