Free Full-Text: Biomarkers for Anti-Angiogenic Therapy in Cancer

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 Conclusions
Anti-angiogenic therapy generally suffers from a high variability in the response by the individual patient. In order to select patients with the highest likelihood for a positive response to such a treatment, the availability of reliable predictive biomarkers for anti-angiogenic therapy will be a key factor. Although there are some promising preliminary results, no general or cancer-specific biomarker has yet emerged, which could help select patients with a positive prognosis for anti-angiogenic
therapy. For its future it is therefore of vital importance to conduct larger systematic trials to translate the preclinical data into clinically usable systems and to switch from unselective therapy to a more
individual drug selection based on the patients’ predispositions."

"Examples for drugs targeting the VEGF-A ligand are Bevacizumab and Aflibercept. Bevacizumab is a VEGF-binding humanized recombinant antibody, which inhibits the VEGF-VEGFR-interaction [44].
In the clinical context it has been used in lung [45–48], breast [49–53], colon [54–58], renal [59,60], gastric [61], pancreatic [62,63], and prostate cancer [64], as well as melanoma [65]. Aflibercept is a
fusion protein of the human Fc part of IgG1 and the extracellular domain of VEGFR. As such it is able to quench VEGF-A and -B, and PlGF-1 and 2, effectively removing the soluble ligands from the VEGF-VEGFR-cascade. So far Aflibercept has been applied in ovarian [66], colorectal [67], lung [68], Int. J. Mol. Sci. 2013, 14 9341 metastatic gynecologic soft-tissue [69], and urothelial metastatic transitional cell cancer [70], as well
as melanoma [71] and glioblastoma [72]."

66. Tew, W.P.; Colombo, N.; Ray-Coquard, I.; Oza, A.; del Campo, J.; Scambia, G.; Spriggs, D. VEGF-Trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC), preliminary results of a randomized, multicenter phase II study. ASCO Meet. Abstr. 2007, 25, 5508

"Ramucirumab, a human antibody specific for the extracellular ligand-binding domain of VEGFR-2, belongs to the class of VEGFR-blocking drugs [73]. Ramucirumab has been used in studies for a multitude of different cancer types and has shown the best results for stable disease (only minor increases or decreases in tumor size) in renal, uterine, colorectal, and ovarian carcinoma [74]."

74. Spratlin, J. Ramucirumab (IMC-1121B), Monoclonal antibody inhibition of vascular endothelial growth factor receptor-2. Curr. Oncol. Rep. 2011, 13, 97–102.