When it comes to cancer, your choices for treatment are many. Cut it out. Break its DNA. Block its unique receptors. Starve its blood supply. For patients, this menu of options may seem comforting or overwhelming; for their doctors and the researchers, it’s a network of possibly conflicting courses of action that must be tailored to each patient, their cancer, and their quality of life. Is it better to do radiation and chemo concurrently or consecutively? What about anti-angiogenic therapy, which slows the growth of blood vessels? Recent data suggests that although anti-angiogenic therapy may be helpful for late stage cancer patients, certain types of angiogenic therapy may be of use in earlier stages of disease.

The blood supply to a typical solid tumor is characterized by wide, dilated blood vessels that are leakier than a normal capillary. Tumor blood vessels are notoriously inefficient—most solid tumors are constantly starved for oxygen, and continuously release angiogenic factors (factors that signal for growth of new blood vessels) to encourage the growth of more blood vessels to serve the tumor’s metabolic demands. One school of metastatic theory holds that the leakiness of the blood vessels may help tumor cells from a primary tumor escape into the circulating blood, and then seed metastases elsewhere in the body. Clearly, this is non-ideal.

Anti-angiogenic therapy seeks to fix this problem by blocking the secreted angiogenic factors and stall the production of more leaky inefficient blood vessels to the tumor. This starves the tumor of its blood supply, and slows its growth considerably. Current anti-angiogenic therapies on the market are recommended primarily for late-stage, post-metastasis cancers, since they slow tumor growth but do not cause regression of the tumor. Although clinical trials are investigating these drugs for use on earlier stage primary tumors, none have been approved for use.

Can tumor angiogenesis be therapeutically targeted earlier in tumor progression? Recent data suggests it might be helpful. A recent paper published in Nature investigates a possible mechanism by which the tumor vasculature becomes abnormal—that is, dilated and leaky. Through genetic manipulation of mice, Dr. Ruth Ganss’ lab created a mouse model of spontaneous pancreatic cancer with normal tumor vasculature. The mice had tumors that received more oxygen more efficiently, and thus grew bigger, faster. However! When they treated the mice with either a cancer vaccine or the mouse’s native immune cells that had been treated to recognize and attack the cancer (a procedure called adoptive transfer), the tumors regressed more quickly than tumors with normal blood vessels, and the mice lived longer. (More details can be found in their paper, located here: http://www.nature.com/nature/journal/v453/n7193/full/nature06868.html)

Dr. Ganss’ lab is primarily focused on how the immune system responds to cancer, so they didn’t test radiation or chemotherapy. However, since both radioisotopes and chemotherapy are blood-borne, it seems logical that improving blood supply to the tumor would increase the amount of on-target therapy delivered.

The money question here is: is there ever a situation in human disease where this strategy would be applicable? Is it possible that a patient would be willing to sacrifice a few weeks of their life to grow a larger tumor that would be more susceptible to therapy? Would the benefits outweigh the risks? This is a unique approach to cancer treatment, somewhat akin to taking a late-stage AIDS patient off their medicine to allow the viral load to repopulate with non-resistant viruses. Further research will inform health care practitioners about the relative success of such a strategy, and I’ll be eagerly following along.