HWN Suggests

Anti-VEGF Therapy in Cancer: A Double-Edged Sword

As they stand now, antiangiogenic therapies face a set of limitations that severally impacts their efficacy. Tumors can acquire resistance to the drugs (if they do not already have intrinsic resistance) and demonstrate an increase in aggressiveness. Moreover, antiangiogenic therapies may cause a decrease in chemotherapy perfusion, lowering the efficacy of chemotherapies given in combination with antiangiogenic medicine. These difficulties suggest that, at least when given alone, antiangiogenic therapies may face severe limitations in survival benefits.

read full article

Featured

 Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy

Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.

Articles of Interest

Angiogenesis Inhibitors

Angiogenesis inhibitors interfere in several ways with various steps in blood vessel growth. Some are monoclonal antibodies that specifically recognize and bind to VEGF. When VEGF is attached to these drugs, it is unable to activate the VEGF receptor. Other angiogenesis inhibitors bind to VEGF and/or its receptor as well as to other receptors on the surface of endothelial cells or to other proteins in the downstream signaling pathways, blocking their activities.

Anti-VEGF Therapies in the Clinic

Taken together, anti-VEGF therapy and anti-angiogenesis therapy are important components of current anti-cancer treatments. However, many issues remain. These include the development and validation of biomarkers that identify those patients most likely to benefit from treatment and the mechanisms underlying primary and acquired resistance. The progress in biomarker development to date highlights both the biological complexity and technical demands of this effort. There are many novel anti-angiogenesis therapies now being developed.

Anti-VEGF/VEGFR Therapy for Cancer: Reassessing the Target

Judah Folkman recognized that new blood vessel formation is important for tumor growth and proposed antiangiogenesis as a novel approach to cancer therapy. Discovery of vascular permeability factor VEGF-A as the primary tumor angiogenesis factor prompted the development of a number of drugs that targeted it or its receptors. These agents have often been successful in halting tumor angiogenesis and in regressing rapidly growing mouse tumors. However, results in human cancer have been less impressive.

Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.