New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?

Giuseppe Bronte, Nicola Silvestris, Marta Castiglia, Antonio Galvano, Francesco Passiglia, Giovanni Sortino, Giuseppe Cicero, Christian Rolfo, Marc Peeters, Viviana Bazan, Daniele Fanale, Antonio Giordano, Antonio Russo

Research output: Contribution to journalArticlepeer-review

Abstract

Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti- EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance.

Original languageEnglish
Pages (from-to)24780-24796
Number of pages17
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 2015

Keywords

  • Cetuximab
  • Colorectal cancer
  • Epidermal growth factor receptor
  • Panitumumab
  • RAS

ASJC Scopus subject areas

  • Oncology

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