Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 May 1;29(5):1108-1119.
doi: 10.1093/annonc/mdy100.

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

S Siena  1 , A Sartore-Bianchi  2 , S Marsoni  3 , H I Hurwitz  4 , S J McCall  4 , F Penault-Llorca  5 , S Srock  6 , A Bardelli  7 , L Trusolino  7
Affiliations
Review

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

S Siena et al. Ann Oncol. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Scenarios for positioning of clinical trials with HER2-targeted treatments in mCRC.
See this image and copyright information in PMC

References

    1. Bertotti A, Papp E, Jones S. et al. The genomic landscape of response to EGFR blockade in colorectal cancer. Nature 2015; 526(7572): 263–267. - PMC - PubMed
    1. Sartore-Bianchi A, Loupakis F, Argilés G. et al. Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory. Ann Oncol 2016; 27(8): 1456–1466. - PubMed
    1. Siravegna G, Marsoni S, Siena S. et al. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 2017; 14(9): 531–548. - PubMed
    1. Bertotti A, Migliardi G, Galimi F. et al. A molecularly annotated platform of patient-derived xenografts (“xenopatients”) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 2011; 1(6): 508–523. - PubMed
    1. The Cancer Genome Atlas Network (TCGAN). Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 330–337. - PMC - PubMed

Publication types

MeSH terms