Antiangiogenic Therapy Understanding the molecular mechanisms that regulate tumor angiogenesis may provide unique opportunities for cancer treatment. Acquired drug resistance of tumor cells due to their high intrinsic mutation rate is a major cause of treatment failure in human cancers. ECs comprising the tumor vasculature are genetically stable and do not share genetic changes with tumor cells; the EC apoptosis pathways are therefore intact. Each EC of a tumor vessel helps provide nourishment to many tumor cells, and although tumor angiogenesis can be driven by a number of exogenous proangiogenic stimuli, experimental data indicate that at least in some. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 18 Antiangiogenic Therapy Understanding the molecular mechanisms that regulate tumor angiogenesis may provide unique opportunities for cancer treatment. Acquired drug resistance of tumor cells due to their high intrinsic mutation rate is a major cause of treatment failure in human cancers. ECs comprising the tumor vasculature are genetically stable and do not share genetic changes with tumor cells the EC apoptosis pathways are therefore intact. Each EC of a tumor vessel helps provide nourishment to many tumor cells and although tumor angiogenesis can be driven by a number of exogenous proangiogenic stimuli experimental data indicate that at least in some tumor types blockade of a single growth factor . VEGF may inhibit tumor-induced vascular growth. Angiogenesis inhibitors function by targeting the critical molecular pathways involved in EC proliferation migration and or survival many of which are unique to the activated endothelium in tumors. Inhibition of growth factor and adhesion-dependent signaling pathways can induce EC apoptosis with concomitant inhibition of tumor growth. Different types of tumors use distinct molecular mechanisms to activate the angiogenic switch. Therefore it is doubtful that a single antiangiogenic strategy will suffice for all human cancers rather a number of agents will be needed each responding to distinct programs of angiogenesis used by different human cancers. Four randomized phase III clinical trials have demonstrated that the addition of bevacizumab Avastin a humanized monoclonal antibody that binds and inhibits VEGF to chemotherapy results in significantly improved response rates progression-free survival and overall survival when compared to treatment with chemotherapy alone Table 80-3 . This effect was shown in the first-line treatment of patients with advanced colon lung and breast cancers and in the second-line treatment of colon cancer. However not all trials have .
