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Cancer Treat Rev. 2016 Dec;51:54-62. doi: 10.1016/j.ctrv.2016.10.006. Epub 2016 Oct 29.

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

Author information

1
Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda, 20162 Milan, Italy.
2
Department of Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda, 20162 Milan, Italy; Department of Oncology, Università degli Studi di Milano, 20122 Milan, Italy.
3
Department of Medical Oncology, Campus Bio-Medico University of Rome, 00128 Rome, Italy.
4
Candiolo Cancer Institute-FPO, IRCCS, 10060 Candiolo, Torino, Italy; Department of Oncology, University of Torino, 10043 Torino, Italy.
5
Department of Medical Oncology, Campus Bio-Medico University of Rome, 00128 Rome, Italy. Electronic address: d.santini@unicampus.it.

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.

KEYWORDS:

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

PMID:
27865140
DOI:
10.1016/j.ctrv.2016.10.006
[Indexed for MEDLINE]

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