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Oncogenic mutations as predictive factors in colorectal cancer

Oncogene volume 29, pages 3033–3043 (2010)Cite this article

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Abstract

The anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies cetuximab and panitumumab have been demonstrated to be new therapeutic options for metastatic colorectal cancer (mCRC). Oncogenic activation of intracellular signalling pathways downstream of EGFR has a major role in colorectal carcinogenesis but has also been reported to be an important mechanism of resistance to anti-EGFR antibodies. Among the activating mutations found in colorectal cancers, tumour KRAS mutations, which are found in ∼40% of the cases, have been widely demonstrated as a major predictive marker of resistance to cetuximab or panitumumab, therefore, opening the way to individualized treatment for patients with mCRC. Other oncogenic mutations, such as BRAF or PIK3CA mutations or loss of PTEN expression, may also be additional interesting predictive markers of response to anti-EGFR monoclonal antibodies but required further evaluation before being incorporated in clinical practice. The identification of these molecular markers involved in the resistance of anti-EGFR antibodies will allow the development of new therapies that should target ‘escape mechanisms’ used by tumours to circumvent a pathway that has been pharmacologically blocked by anti-EGFR.

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Acknowledgements

We thank Institut National du Cancer (N°2009-1-RT03) and the Region Ile de France for their financial support.

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Authors and Affiliations

  1. INSERM UMR-S 775 Molecular Basis of Response to Xenobiotics, Paris, France

    A Lièvre, H Blons & P Laurent-Puig

  2. Assistance-Publique Hôpitaux de Paris, Hôpital Ambroise Paré, Service d’Hépato-Gastroentérologie et Oncologie Digestive, Boulogne-Billancourt, France

    A Lièvre

  3. Université Versailles Saint-Quentin-en-Yvelines, Versailles, France

    A Lièvre

  4. Université Paris Descartes, Paris, France

    H Blons & P Laurent-Puig

  5. Assistance-Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Paris, France

    H Blons & P Laurent-Puig

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  1. A Lièvre
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  2. H Blons
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Correspondence to P Laurent-Puig.

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Competing interests

P Laurent-Puig received compensation as a member of the advisory board of MerckSerono and Amgen company. His research was in part sponsored by MerckSerono and Myriad Genetics. Dr Lievre has consulted for Merck and received compensation. Dr Blons declares no conflict of interest.

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Lièvre, A., Blons, H. & Laurent-Puig, P. Oncogenic mutations as predictive factors in colorectal cancer. Oncogene 29, 3033–3043 (2010). https://doi.org/10.1038/onc.2010.89

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  • DOI: https://doi.org/10.1038/onc.2010.89

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