Elise C. Kohn, MD [ View bio ] (National Cancer Institute)
Since the seminal observations of Judah Folkman and Lance Liotta that vascular development, angiogenesis, is necessary for tumor growth and metastasis, the field has blossomed. We now recognize that the interplay between the normal, activatable, vascular and lymphovascular systems and the premalignant, malignant, and invasive cancer is a key element to the progression of cancer. Likewise, angiogenesis is important in promoting other pathologies, as well as being necessary for prevention of others. As such, it has become a field critically translated into clinical application.The field of targeted cancer therapeutics was initiated with anti-angiogenic agents and this class of agents continues to both expand and yield successes. Angiogenesis factors and receptors are the most successful targets not specifically related to a mutational genetic event in cancer. Early preclinical data built upon the recognition of the central role of VEGF in tumor growth and dissemination, proving the need for vasculature for delivery of nutrients and as a conduit for tumor cell dissemination. Additional roles including trophic effects on the immune system, and secondary effects on the other stromal elements further reinforce this target.
The two most common classes of anti-angiogenic therapeutics are neutralizing antibodies/peptibodies and kinase inhibitors. These have been developed successfully to either approval and/or advanced clinical investigation for VEGF, angiopoeitin 1/2, VEGFR1/2/3, as well as targets that affect angiogenesis but also other stromal and epithelial targets such as PDGFR, CSF1R, kit, src, fak, and other kinases. FDA and/or EMA approvals have been given for several agents for solid tumor treatments alone and/or in combinations. Current clinical cancer research addresses optimal use of anti-angiogenics, anti-angiogenic combinations, combinations with chemotherapy, timing of treatment, novel targets in angiogenesis and lymphangiogenesis, and consideration for prevention use for selected cancers.
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