Targeting vascular endothelial growth factor pathway in first-line treatment of metastatic colorectal cancer: state-of-the-art and future perspectives in clinical and molecular selection of patients.
Targeting vascular endothelial growth factor (VEGF) pathway represents a successful strategy in the treatment of metastatic colorectal cancer (mCRC). Since the approval of the first antiangiogenic drug, the anti-VEGF monoclonal antibody bevacizumab, a number of other molecules have been tested in preliminary trials and are currently under investigation in phase III randomized studies. At present, no clinical tools are available to select patients more likely to benefit from VEGF pathway inhibitors nor to exclude those who are proner to suffer from specific adverse events, so that almost all mCRC patients are potentially candidate to receive an antiangiogenic-containing regimen. To overcome this substantial limit, a consistent aid is awaited by the identification of molecular tools of selection. Retrospective analyses and translational studies have been conducted and are currently ongoing to address this major question, investigating molecular, biological and genetic markers. This review aims at resuming the state-of-the-art about the role of VEGF pathway inhibitors in the treatment of mCRC and at focusing on the present knowledge about candidate biomarkers as predictors of activity and toxicity.
Loupakis
Fotios
F
Division of Medical Oncology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Italy. fotiosloupakis@gmail.com
Bocci
Guido
G
Pasqualetti
Giuseppe
G
Fornaro
Lorenzo
L
Salvatore
Lisa
L
Cremolini
Chiara
C
Masi
Gianluca
G
Danesi
Romano
R
Del Tacca
Mario
M
Falcone
Alfredo
A
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D006801:Humans; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018579:Patient Selection; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042442:Vascular Endothelial Growth Factors; D000068258:Bevacizumab