Adam P. Dicker, M.D., Ph.D.

Anti-Angiogenesis research

A new area of cancer research that has generated great excitement in recent years and that may be used in conjunction with radiotherapy is the use of angiogenesis inhibitors. These are drugs that block the proliferation of new blood vessels, a process known as angiogenesis (see graphic above). In order for tumors to grow, they require new blood vessels to deliver oxygen and nutrients. By blocking the formation of new vessels, researchers believe they may be able to starve the tumor. Since angiogenesis inhibitors are cytostatic (preventing the growth of a tumor) rather than cytotoxic (killing the tumor), they will most likely be used in conjunction with chemotherapy or radiation therapy as a cancer treatment.

One of the anti-angiogenesis agents being tested at Jefferson is thalidomide, the same drug that was widely given, with disastrous results, to pregnant women in the 1950s as a treatment for morning sickness. Thalidomide was withdrawn from the market when it was shown to cause severe birth defects. But in 1994, researchers demonstrated that the very properties that damaged the developing fetus, that is, inhibition of new vessel growth, could be used therapeutically to starve tissues such as tumors. An RTOG-sponsored clinical trial of thalidomide used in conjunction with radiotherapy as a treatment for brain glioma is now underway (see article at left), with Jefferson's Adam Dicker chairing the correlative studies section of the trial.

Dicker explained that angiogenesis, as measured by the density of microvessels (the MVD) in a given area, has been shown in many studies to correlate with tumor extent, aggressiveness, decreased survival, and lymph node metastases. A landmark paper in 1991 showed that in a study of women with breast cancer, all patients with microvessel counts over a certain threshold developed metastases. "This was the precedent for thinking, well, if there's increased angiogenesis in patients with more advanced disease, then presumably if you impact on the angiogenesis you might impact on the overall progression of the disease," said Dicker, who is collaborating on research with George Iliakis, Ph.D., Professor and Director of the Radiobiology Division.

Another reason for the excitement about angiogenesis inhibitors is that preclinical data indicates little likelihood that tumors will develop resistance to these agents. "It takes a long time for these anti-angiogenesis agents to have an effect," Dicker notes, "but they have a very durable length of response.