By Nik Sutter
MADISON – A new drug created by UW-Madison scientists in collaboration with Colby Pharmaceuticals may pave they way to successful prevention and treatment of prostate cancer. With a current lack of investment support for men’s health research, however, getting the drug to the critical clinical-trial phases remains a challenge.
Last month, Colby Pharmaceuticals wowed a panel of venture capitalists and angel investors at the Wisconsin Early Stage Symposium, earning a crown as one of the four winners of the “Elevator Pitch Olympics.” For Colby’s breakthrough drug, called MDL, and three other drugs active against prostate cancer in the pipeline, this meant far more than simply a trophy or plaque.
“Winning the ‘Elevator Pitch’ was extremely important to us,” said Dr. Hirak Basu, of the UW-Madison’s Paul P. Carbone Comprehensive Cancer Center in Madison, and the co-founder and Chief Scientific Officer of Colby. “We gained some direct connections to Midwest investors who are seriously interested in reviewing our business plan. We hope that by securing some seed funding, we can take at least one of our drugs to clinical trial.”
More than 25 Wisconsin firms seeking private equity competed during the two-day symposium. Each company had 90 seconds to pitch their entrepreneurial start-up to a panel of venture capitalists and angel investors, who judged them based on how their pitches would have compelled the panel of investors to establish a meeting or read further into the business plan.
According to Basu, results of two new drugs, including MDL, have been promising enough to justify immediate testing through clinical trials. Research of this drug is built on the established fact that oxygen-free radical production in the prostate drives the progression, and in many cases the occurrence of prostate cancer.
Until recently, Basu said, it has been unclear why the oxygen-free radicals were high in the prostate gland. Using human prostate cancer cell lines and genetically engineered mice susceptible to development of prostate cancers, UW scientists have previously shown that increases in the sex-hormone androgen mark the start of this process. This androgen signaling causes many things, among which is an increase in oxygen-free radicals, which are known to play a key role in cell signaling and prostate cancer development.
Basu and his colleagues have recently discovered that androgen causes this oxygen free radical formation in the prostate by oxidizing polyamines, which are produced in very high amount by the prostate gland and are an essential component of the semen of all mammals including human.
“The discovery of this pathway is a major step forward in understanding the role of androgen in prostate cancer development” Basu said.
Basu also described a small molecule enzyme inhibitor MDL to block the polyamine oxidation pathway, reduce the oxygen-free radical formation in the mouse prostate gland and significantly delayed tumor formation in genetically engineered mice that develop spontaneous prostate cancer.
To the best of Basu’s knowledge, this is the first report of a specific enzyme inhibitor that blocks androgen-induced oxidative stress in the prostate and prevents spontaneous prostate tumor development.
Several more tests need to be performed, but researchers including world-renowned prostate cancer clinician Dr. George Wilding, director of the UW Cancer Research Center and a co-inventor of the pathway, hope that with proper fund support phase 1 clinical trials of MDL may start within a year and a half.
Colby Pharmaceuticals is not concentrating solely on the polyamine oxidation and prostate tumor progression. In addition to MDL, Colby currently has three other drugs in the pipeline that can affect the androgen signaling pathway, androgen independent tumor proliferation pathway and the oxidative stress generating pathway subsequent to polyamine oxidation.
“Thus, we can not only prevent prostate cancer progression, but probably can treat the tumors that have progressed to the more virulent androgen independent state for which there is exists no effective treatment,” Basu said.
If MDL reaches clinical trials, men with prostate cancer may only be catching a glimpse into the doorway of future research developments.
“If we can successfully block these pathways and reduce prostate cancer recurrence in men, we will probably push to fund a chemoprevention study where all high-risk men can be given the drug to reduce prostate tumor occurrence,” Basu said. “However, that’s a very long and expensive trial.”
Sutter is a student in the UW-Madison Department of Life Sciences Communication.