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

  • Marta MartinsEmail author
  • André Mansinho
  • Raquel Cruz-Duarte
  • Soraia Lobo Martins
  • Luís Costa
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

Colorectal cancer Epidermal growth factor receptor Primary resistance Secondary resistance Targeted therapy 

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Marta Martins
    • 1
    Email author
  • André Mansinho
    • 2
  • Raquel Cruz-Duarte
    • 1
  • Soraia Lobo Martins
    • 2
  • Luís Costa
    • 1
    • 2
  1. 1.Instituto de Medicina Molecular – João Lobo Antunes, Faculty of MedicineUniversity of LisbonLisbonPortugal
  2. 2.Oncology Division, Santa Maria HospitalCentro Hospitalar Lisboa NorteLisbonPortugal

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