Dysregulated Angiogenesis in Cancer

Mark Socinski, MD: One of the hallmarks of cancer is the ability of a growing tumor mass to induce angiogenesis. It’s critical to the lifecycle of the tumor. The cancer cells, when they get stressed by hypoxia or other oxidative stress, begin to secrete pro-angiogenic ligands that stimulate endothelial cells in their supporting structure to begin the process of neoangiogenesis, or blood vessels growing into the cancer to supply them with the oxygen and nutrients that they need. This mechanism is critical to tumor survival.

The dominant proangiogenic factor is vascular endothelial growth factor (VEGF), but there are other pro-angiogenic growth factors that are known. Again, this induces genetically stable and genetically normal endothelial cells to begin the process of angiogenesis, which is, in this case, a very dysregulated or primitive angiogenic strategy relative to normal anti-angiogenesis.

We know that angiogenesis is critical to maintaining self. If we have a wound or an incision in surgery, we need to cure that and we need to heal; so angiogenesis is part of our normal makeup, and we have a number of balancing mechanisms for angiogenesis. But with regard to the cancer, what the cancer is interested in is getting oxygen and nutrients, so it has this mechanism. And understanding this has really created a number of therapeutic targets that we’ve manipulated for the advantage of our patients.

In tumor-induced angiogenesis, the blood vessels tend to be very tortuous. They don’t have the most competent supporting structures, so we refer to them as leaky vessels. Or there’s a great deal of permeability in these sorts of vessels. In fact, VEGF was initially named vascular permeability factor, so you can understand where that comes from.

Obviously, angiogenesis is also key to the pathway that cancers use to gain access to the vascular system to metastasize. Obviously, as an oncologist, we’re mostly dealing with the impact of metastatic disease, and, again, this process of angiogenesis is important. Inhibition of angiogenesis allows tumor vasculature to normalize somewhat. It tends to decrease vascular pressure in tumors. It allows, theoretically, chemotherapy to have better access to tumors. R

Transcript Edited for Clarity