Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and other Hematologic and Solid Malignancies

K.      Podar; K.      C. Anderson

doi:10.2174/156800911798073113

Abstract

Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti- VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical and clinical anti-cancer activity, they prolong overall survival of cancer patients for only months, followed by a restoration of tumor growth and progression. Therefore, there is a clear need to increase our understanding of tumor angiogenesis and the development of resistance. In this review we discuss up-to-date knowledge on mechanisms of tumor angiogenesis, and summarize preclinical and clinical data on existing and potential future anti-angiogenic agents and treatment strategies for Multiple Myeloma (MM) and other hematologic and solid malignancies.

Keywords: AMG-386, AVE8062, axitinib, bevacizumab, CDP860, CE-245677, CEP-11981, cilengitide, combretastatin, CP-868, 596, enzastaurin, exherin, HuMV833, lenalidomide, metronomic chemotherapy, MN-029, OMP-21M18, pazopanib, PF-4856884, pomalidomide, Reg421, semaxanib, sorafenib and sunitinib, TB403, thalidomide, TZT-1027, vadimezan, vandetanib, vatalanib, VEGFR antibodies, VEGF-trap, ZD6126