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Targeting Angiogenic Pathways in Colorectal Cancer: Complexities, Challenges and Future Directions
- 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.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Oncology
medicine.medical_specialty
Bevacizumab
Pyridines
Angiogenesis
Colorectal cancer
Recombinant Fusion Proteins
Clinical Biochemistry
Angiogenesis Inhibitors
Disease
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Regorafenib
Drug Discovery
medicine
Humans
Molecular Targeted Therapy
Neoplasm Metastasis
Aflibercept
business.industry
Phenylurea Compounds
medicine.disease
Survival Analysis
Clinical trial
Vascular endothelial growth factor
Receptors, Vascular Endothelial Growth Factor
Treatment Outcome
030104 developmental biology
Clinical Trials, Phase III as Topic
chemistry
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Molecular Medicine
Colorectal Neoplasms
business
Signal Transduction
medicine.drug
Subjects
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