Multitargeted Tyrosine Kinase Inhibitors: When Are More Targets Necessary?

Faculty:

Lee S. Rosen, MD

Learning Objectives

Upon completion of this activity, participants should be able to:

• Describe the role of vascular endothelial growth factor (VEGF) in tumor growth and survival
• Identify emerging targeted therapies that have shown activity in the treatment of a various solid tumors
• List differentiating factors between monoclonal antibodies and small-molecule kinase inhibitors targeting the VEGF pathway
• Describe the rationale behind the use of kinase inhibitors that target multiple pathways

Topics covered include:

• Introduction: Targeting Tumors by Inhibiting Angiogenesis
• VEGF Is a Key Mediator of Tumor Angiogenesis
• Summary of the Proposed Mechanisms of Action of Anti-VEGF Agents
• Targeting VEGF: The Efficacy of Bevacizumab in Multiple Tumor Types
• Combining Bevacizumab With Other Targeted Therapies
• Targeting VEGF: The VEGF Trap as a Potent Angiogenesis Inhibitor
• Toxicity Associated With Targeting VEGF
• Targeting VEGF: Multitargeted Agents May Increase Activity at the Cost of Toxicity
• Sunitinib Tyrosine Kinase Inhibitor Targets Multiple Receptors
• Sorafenib Tyrosine Kinase Inhibitor Targets Raf Kinase and VEGF Receptors
• Motesanib Tyrosine Kinase Inhibitor Targets VEGF Receptors, c-Kit, and PDGFR
• Other Multitargeted Tyrosine Kinase Inhibitors Currently in Development
• Conclusions