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

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.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Sartore-Bianchi A,Siena S,Tonini G,Bardelli A,Santini D

doi

10.1016/j.ctrv.2016.10.006

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

54-62

eissn

0305-7372

issn

1532-1967

pii

S0305-7372(16)30106-2

journal_volume

51

pub_type

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