Cutting tumor supply lines may boost cancer treatments, UF professor says

Scientists have long viewed the network of blood vessels tumors create to siphon oxygen and other nutrients from the body as a potential target for therapies geared toward stopping tumors in their tracks. But efforts to block blood vessel development or impede existing vessels in tumors in the lab haven’t met with as much success as some had hoped.

Now Dietmar W. Siemann, Ph.D., a University of Florida researcher who reviewed findings from published studies that tested a class of drugs known as vascular disrupting agents — designed to disrupt blood flow to tumors — says using them in combination with chemotherapy, radiation or heat appears to be more effective than using them alone.

“Agents designed to directly attack tumor blood vessels provide a new approach to significantly improve the effectiveness of radiotherapy and chemotherapy in cancer treatment,” said Siemann, a professor in the department of radiation oncology at the UF Shands Cancer Center.

Siemann will publish a paper describing the results of his review, which sought to determine the effectiveness of these drugs to date on the basis of findings from preclinical studies, in the May 10 online edition of CANCER, the journal of the American Cancer Society.

He collaborated with researchers from Aarhus University in Denmark and Boston’s Oxigene Inc., which manufacturers one such drug.

The authors found that vascular disrupting agents interfered with existing blood vessels and cut tumor blood flow in animals and human tumors studied in a laboratory setting. Most of the tumor tissue died, but the drugs — which home in on immature blood vessels the tumor forms but spare normal vessels — were not able to destroy all tumor cells. Using chemotherapy, radiation or heat in combination with the drugs, however, led to better results, Siemann said.

The concept of using drugs to interfere with and halt new blood vessel growth was pioneered in animal research by Judah Folkman, M.D., a cancer researcher at Harvard University. The late Juliana Denekamp, Ph.D., of Umea University, Sweden, is credited with developing the idea to use vascular targeting agents to directly damage blood vessels and thereby kill tumor cells by starving them of nutrients. Their findings, which gained national attention in 1998, inspired thousands of follow-up studies.

At a national medical conference last year, Siemann reported he and other UF scientists significantly delayed the growth of cancerous human tumors in mice by combining a drug that thwarts blood vessel formation with a vascular disrupting agent that destroys existing vessels. Siemann added that more extensive research is needed to determine whether the beneficial effects observed in mice and in tissues studied in the laboratory can be duplicated in human cancer patients. He and his research team recently received a $1.2 million, four-year grant renewal from the National Cancer Institute to continue his studies.