Overcoming dynamic molecular heterogeneity in metastatic colorectal cancer: Multikinase inhibition with regorafenib and the case of rechallenge with anti-EGFR

Andrea Sartore-Bianchi, Salvatore Siena, Giuseppe Tonini, Alberto Bardelli, Daniele Santini

Research output: Contribution to journalReview articlepeer-review

Abstract

In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade. In chemorefractory patients, multikinase inhibition with regorafenib has proved to be effective and rechallenge with chemotherapy or anti-EGFR agents is empirically pursued. This review will critically discuss how the evolving knowledge of mechanisms of resistance driven by intratumoural dynamic molecular heterogeneity can impact on rational choice of treatments in this setting.

Original languageEnglish
Pages (from-to)54-62
Number of pages9
JournalCancer Treatment Reviews
Volume51
DOIs
Publication statusPublished - Dec 1 2016

Keywords

  • Clonal evolution
  • Drug resistance
  • EGFR
  • Metastatic colorectal cancer
  • Rechallenge therapy
  • Regorafenib

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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