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Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions

Authors :
David Cunningham
Khurum Khan
Ian Chau
Source :
Current Drug Targets. 18:56-71
Publication Year :
2016
Publisher :
Bentham Science Publishers Ltd., 2016.

Abstract

Colorectal cancer (CRC) is one of the commonest cancers in the world. During the last decade, the development of targeted therapies has given cancer treatment a novel direction in management of metastatic CRC (mCRC) and has enriched the therapeutic armamentarium in the management of this disease. In mCRC, targeting angiogenesis via the vascular endothelial growth factor (VEGF) pathway has been of particular interest based on the favourable survival benefit demonstrated by bevacizumab in clinical trials. More recently, large phase III studies have shown clinical efficacy for the new antiangiogenic agents aflibercept and regorafenib. However, the results of pre-clinical and clinical studies of other anti-angiogenic agents have been disappointing. Furthermore, the benefits from angiogenic inhibitors (AIs) in an unselected patient population are modest. Research into predictive biomarkers is therefore essential, but has, to date, been unsuccessful. Nevertheless, aflibercept and regorafenib have been shown to benefit both bevacizumab naive and refractory patients, suggesting that acquired resistance to AIs can be potentially reversed. This review describes the most recent advances in development of AIs in mCRC with particular focus on aflibercept and regorafenib, the existing challenges for the evaluation of these agents in clinical practice and potential strategies in designing clinical trials that could lead to the discovery of clinically meaningful biomarkers.

Details

ISSN :
13894501
Volume :
18
Database :
OpenAIRE
Journal :
Current Drug Targets
Accession number :
edsair.doi.dedup.....d6a09f1cae6fdd9e3755831c66ac682f
Full Text :
https://doi.org/10.2174/1389450116666150325231555