Blood Vessel Growth Slowed with Common Chemotherapy Drugs, Slow Spread of Cancer

A new discovery at the Johns Hopkins University School of Medicine has shown commonly used chemotherapy drugs can slow the spread of some cancers.

Widely used chemotherapy drugs such as doxorubicin (Adriamycin), daunorubicin, epirubicin, idarubicin, all members of the class anthracycline, have been used to treat cancers such as leukemia, lymphoma and other carcinomas for forty years. Typically the drugs were given in extremely large doses every few weeks to kill the quickly growing cancer cells and prohibit them from spreading.

"But the late Judah Folkman discovered in 2000 that so-called metronomic treatment, giving patients lower doses of these drugs more frequently, can keep cancer growth at bay by blocking blood vessel formation, but the exact mechanism by which this occurred wasn't known," says Gregg L. Semenza, M.D., Ph.D., director of the vascular program at the Johns Hopkins Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine. "Now we've shown how it happens and what players are involved, which could help shape future clinical trials for patients with certain types of cancers."

The HIF-1 protein has been studied by Semenza and his colleagues for many years and they have determined the protein assists the body with new blood vessel growth. In an effort to figure out how to stop the blood vessel growth, and therefore prohibit the growth of tumors, the team tested thousands of FDA-approved cancer drugs. The tests showed no effect on HIF-1 protein but showed promise in the area of DNA binding.

"We know that this class of drug prefers to bind to DNA sequences that are similar to the DNA sequence bound by HIF-1, but this is the first direct evidence that anthracyclines prevent HIF-1 from binding to and turning on target genes," says Semenza.

After several tests were performed on mice with tumors grown from human prostate cancer cells, the team discovered positive results in regards to blood vessel formation.

"What this means, we hope, is that patients with a prostate cancer that has high HIF-1 levels - which puts them at greater risk of relapse following surgery or radiation therapy - might benefit from treatment with these drugs," says Semenza. "However, clinical trials are necessary to determine whether this approach will help keep cancer patients alive."

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