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Anti-EGFR Therapy to Treat Metastatic Colorectal Cancer: Not for All

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Targeted Therapy of Colorectal Cancer Subtypes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1110))

Abstract

The development of monoclonal antibodies (mAbs) cetuximab and panitumumab, which target the transmembrane protein epidermal growth factor receptor (EGFR), mark a major step forward in the treatment of metastatic colorectal cancer (mCRC). However, this therapeutic progress proved to be effective only in a very restricted subset of patients. Although several mechanisms of resistance, both primary and acquired, have been identified, the only established predictive tumour biomarker for the treatment of mCRC patients is the RAS mutational status. RAS activating mutations predict a lack of response to these therapies while low levels of primary resistance characterize RAS wild type (WT) patients (only about 15%). However, even WT patients that initially respond to anti-EGFR therapy, eventually undergo tumour progression. In this context, there is still more to be done in the search for effective predictive markers with therapeutic applicability. In this chapter, we provide an overview on the mechanisms that contribute to resistance to EGFR-targeted therapy and highlight what is still missing in our understanding of these molecular mechanisms and approaches to overcome them.

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Authors and Affiliations

  1. Instituto de Medicina Molecular – João Lobo Antunes, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    Marta Martins, Raquel Cruz-Duarte & Luís Costa

  2. Oncology Division, Santa Maria Hospital, Centro Hospitalar Lisboa Norte, Lisbon, Portugal

    André Mansinho, Soraia Lobo Martins & Luís Costa

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  1. Department of Human Genetics, National Health Institute ‘Dr. Ricardo Jorge’, Lisbon, Portugal

    Peter Jordan

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Martins, M., Mansinho, A., Cruz-Duarte, R., Martins, S.L., Costa, L. (2018). Anti-EGFR Therapy to Treat Metastatic Colorectal Cancer: Not for All. In: Jordan, P. (eds) Targeted Therapy of Colorectal Cancer Subtypes. Advances in Experimental Medicine and Biology, vol 1110. Springer, Cham. https://doi.org/10.1007/978-3-030-02771-1_8

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