Anti-Angiogenics: Their Value in Colorectal Cancer Therapy

Autor: Andreas Seeber, Eberhard Gunsilius, Günther Gastl, Andreas Pircher
Rok vydání: 2018
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Bevacizumab
Colon
Angiogenesis
Colorectal cancer
Angiogenesis Inhibitors
Ramucirumab
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Regorafenib
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Tumor
Tumor Microenvironment
medicine
Humans
Molecular Targeted Therapy
Protein Kinase Inhibitors
Randomized Controlled Trials as Topic
Aflibercept
Tumor microenvironment
Neovascularization
Pathologic
business.industry
Patient Selection
Rectum
Hematology
medicine.disease
Vascular endothelial growth factor
Treatment Outcome
030104 developmental biology
Clinical Trials
Phase III as Topic
chemistry
030220 oncology & carcinogenesis
Colorectal Neoplasms
business
Signal Transduction
medicine.drug
Zdroj: Oncology Research and Treatment. 41:188-193
ISSN: 2296-5262
2296-5270
DOI: 10.1159/000488301
Popis: Angiogenesis is a hallmark of cancer and is regulated by a balance of pro- and anti-angiogenic factors; among them, the vascular endothelial growth factor (VEGF) is the key angiogenic factor. VEGF plays an important role in colorectal cancer (CRC) biology, and its inhibition by using bevacizumab, an anti-VEGF antibody, proved for the first time to be effective and became indispensable for the treatment of metastatic CRC (mCRC). Several large phase III studies showed also relevant responses and tolerability of other anti-angiogenic drugs such as ramucirumab, aflibercept, and regorafenib, and led to the approval of these therapeutics. Nevertheless, the efficacy of anti-angiogenic therapies is rather limited and the high expectations raised by preclinical studies were not fulfilled in the clinics. Furthermore, to date, no predictive biomarkers for anti-angiogenic agents could be identified and validated. Thus, new mechanisms of action are discussed, such as tumor vasculature normalization to improve the accessibility of tumor tissue by drugs or to promote tumor infiltration by host immune cells. Cellular and molecular studies will be necessary to characterize the dynamic changes of the tumor microenvironment and the vascular architecture in individual patients in order to predict responsiveness to anti-angiogenic therapies. In this review, we tried to highlight the standard of care of using anti-angiogenics in mCRC patients and to provide an outlook on potential new substances and strategies.
Databáze: OpenAIRE
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