Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions.
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Date
2017-01Author
Khan, K
Cunningham, D
Chau, I
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Colorectal Neoplasms
Neoplasm Metastasis
Phenylurea Compounds
Pyridines
Receptors, Vascular Endothelial Growth Factor
Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A
Recombinant Fusion Proteins
Treatment Outcome
Survival Analysis
Signal Transduction
Drug Resistance, Neoplasm
Clinical Trials, Phase III as Topic
Molecular Targeted Therapy
Research team
Medicine (RMH Smith Cunningham)
Language
eng
Date accepted
2016-03-24
License start date
2017-01
Citation
Current drug targets, 2017, 18 (1), pp. 56 - 71