UC San Francisco researchers may have determined how the experimental anti-cancer drug ONYX-015 succeeds in killing cancer cells, offering a possible answer to recent questions about its mechanism of action and providing insight that could contribute to a deeper understanding of cancer biology.
The finding, reported by Frank McCormick, Ph.D., F.R.S., director of the UCSF Cancer Research Institute, at the American Association for Cancer Research (AACR) annual meeting in Philadelphia, could solidify and improve efforts to use the drug, now in phase II clinical trials. It could also lead to modified approaches for killing cancer cells with tumor-specific viruses.
ONYX-015 has shown promising results in phase II clinical trials of patients with head and neck cancer (to be reported by Onyx Pharmaceuticals, Inc. at AACR), and phase II trials have opened for patients with colon, pancreatic and ovarian cancer. (Phase II trials are small-scale studies designed to determined effective dosage.)
But recent findings in several laboratories have brought into question the presumed mechanism of action of this potent agent, a genetically engineered version of the cold virus known as adenovirus. The observations have indicated that the virus, while effective in its manipulated form against one large class of tumor cells, might also be able to kill other tumor cells, apparently by an unknown mechanism.
The observations have raised concerns that the drug could harm normal cells in humans and have presented the slight possibility that the drug could be used against a broader range of tumor cells than previously thought. More fundamentally, they have raised questions about the regulation of a particular gene, known as p53, in the pathway toward cancer.
The p53 gene plays a key role in preventing cells from slipping into
uncontrolled cell growth, a hallmark of cancer. And the ability of various
factors to disable the gene accounts for 60 percent of malignant tu
'"/>
Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
14-Apr-1999