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Protein Linked to Half of All Cancers

by Brendon Nafziger, DOTmed News Associate Editor | October 09, 2009
A promising finding
for cancer research
Research presented this week at a British cancer conference could lead to revolutionary new anti-cancer drugs.

The findings, presented by Sir David Lane, chief scientist of the charity Cancer Research UK, focus on a protein, known as p 53, thought to be involved in about half of all cancers.

The studies shown to the National Cancer Research Institute Cancer Conference in Birmingham, England on Tuesday were conducted by Dr. Dimitris Xirodimas, a researcher at the University of Dundee.

In the studies, Dr. Xirodimas and his team figured out why a commonly used chemotherapy drug and antibiotic, Actinomycin D, works: it appears to block a process which holds back the activation of p 53.

Promise of p 53

"P 53 has been of interest since the late '80s and early '90s," William Phelps, M.D., director of translational and preclinical cancer research at the American Cancer Society, tells DOTmed News, "when it became apparent that it was the most commonly mutated gene across all cancers."

Dr. Phelps further explains that "p 53 [is a] kind of a master regulator of cells." Its capacity to control growth makes the tiny protein a tumor's worst foe: once triggered, it repairs DNA in rogue cells, and if that doesn't work, it stops them from growing or simply kills them altogether.

But it seems that in many cancerous cells something is holding p 53 back. Dr. Xirodimas and his group believe it is the process called NEDDylation.

NEDDylation frustration

In NEDDylation, NEDD8, a molecule, gloms onto signaling proteins called ribosomal proteins, trapping them in part of the cell's nucleus. Once trapped, these ribosomal proteins can't deliver the message to p 53 to inhibit the cell's growth or kill it off.

In his studies, Dr. Xirodimas found that Actinomycin D appears to work by interfering with NEDDylation. This allows the ribosomal proteins to make a dash for it and activate p 53, so it can wipe out the cancer.

In the pipeline

Dr. Phelps believes studies like Dr. Xirodimas', by helping us understand the mechanisms behind NEDDyltation, will aid future efforts to make drugs targeting these actions.

And drugs specifically designed to interrupt NEDDYlation are in the works. Millennium Drugs, a biotech company based in Boston, that makes the cancer drug Velcade, has a NEDD8-acting drug in the pipeline, known as MLN4924.

According to Lauren Musto, a spokesperson for Millennium, results from animal tests on the drug were presented at the ASCO conference last June, and it entered Phase 1 human trials in August. The company is seeing how it fares against solid tumors.

It's still some time away from real clinical use, though. "We don't anticipate having any results for another year or two," Musto tells DOTmed News.