Temple University researchers develop new targeted cancer therapy

Temple University researchers have developed a new drug that halts cancer cell division, instigating tumor death. The drug works by interfering with the activity of a gene called Plk1 and is now in phase I clinical trials for human cancer therapy. Their research is published in the March issue of Cancer Cell.

Plk1 is one of several molecules that play a critical role in the spread of cancer. Previous studies have found higher levels of Plk1 in cancer tumors and in patients with poorer survival rates. When Plk1 activity was blocked, cancer cells could not divide and tumors could not survive.

Led by Prem Reddy, Ph.D., professor of biochemistry and director of the Fels Institute for Cancer Research at Temple University School of Medicine, the Temple team sought out a new compound that would target and block Plk1. They developed and tested ON01910, a small molecule that inhibits Plk1 activity, on 94 different human cancers. "We found that ON01910 was a potent inhibitor of human tumor growth and also worked well with several existing cancer drugs, often inducing complete regression of tumors. Someday it might work either as a single drug or in combination with other drugs," said Reddy.

Johns Hopkins Medicine and Mt. Sinai Medical Center are currently conducting the first clinical trial of ON01910 in patients with advanced and metastatic cancers. The studies will evaluate data from up to 56 patients. ON01910 is known as a targeted therapy, a new area of cancer drug research and development. As the name suggests, such therapies target molecules that are critical to a tumor's survival. Targeted therapies block the molecules from functioning, thereby preventing tumors from surviving.

On the unique actions of ON01910, Reddy said, "Our drug stops tumor cells from reaching normal cells three ways. First, it blocks invasion, next it blocks angiogenesis and finally, it induces tumor cell death. It also appears to be very safe." Other research team members are Kiranmai Gumireddy1, M.V. Ramana Reddy, Stephen C. Cosenza1, R. Boomi Nathan, Stacey J. Baker, Nabisa Papathi1, Jiandong Jiang, and James Holland.

For a copy of the study, "ON01910, a non-ATP competitive small molecule inhibitor of Plk1, is a potent anticancer agent," contact Heidi Hardman at Cancer Cell 617-397-2879 or go to EurekAlert! http://www.eurekalert.org/jrnls/cell/pages/index.php.

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