Cancer Insights: Potential new way to target lethal prostate cancer

August 31, 2015 | by Sumanta Kumar Pal M.D.

More than 2.9 million men living in the U.S. today have been diagnosed with prostate cancer. Many of these men have had treatment with surgery or radiation and will never see their cancer return, giving hope to the roughly 220,800 people who will be diagnosed with prostate cancer this year. Unfortunately, for a significant percentage of patients with prostate cancer, the disease remains highly lethal. Prostate Cancer Awareness Month is an ideal time to shift focus to these men.

Sumanta Pal, M.D. Sumanta Kumar Pal

One of the key unknowns facing doctors, researchers and, of course, patients comes when trying to determine whether a highly curable cancer might turn lethal. Novel gene-profiling techniques offer clues about which prostate cancers appear to be more aggressive, but these tests are far from definitive. Furthermore, many of these tests rely on a biopsy of the prostate, a painful procedure laden with risks such as infection and bleeding. That could change. Jeremy Jones, Ph.D., a City of Hope scientist, is developing an alternative testing approach known as a “liquid biopsy.”

“The liquid biopsy simply involves taking a small sample of blood,” Jones said. “We now have the technology to pull from blood some of the same information we would get from cancer tissue.”

In April, Jones presented his work at the 2015 American Association of Cancer Research Meeting in Philadelphia. His project involved analyzing blood samples he had collected from patients receiving treatment at City of Hope for prostate cancer that had spread to the bone and other organs.

“From the blood we collected, we were able to generate a heat-map that delineates which genes are turned on or off,” Jones said. “It’s early, but we are starting to see certain genes that may potentially drive growth of prostate cancer and possibly even resistance to existing therapies.”

Jones is working diligently to expand his efforts and confirm the value of these liquid biopsies. He also has his sights set on developing new drugs for patients with advanced prostate cancer. While the past decade has been marked by a slew of new drug approvals for the disease, each adds only several months of projected lifespan. Jones has found a means of blocking the principal protein that drives prostate cancer, called the androgen receptor, by modifying an existing drug called pyrivinium.

“We did a very elaborate screen of many drugs to identify which would block the androgen receptor best,” Jones said. “I think we were all surprised to find it was pyrvinium. After all, the drug was developed to treat intestinal worms."

As Jones’ published work has shown, pyrvinium and its derivatives do much more than fight intestinal worms. They also attack the androgen receptor in a manner distinct from any Food and Drug Administration-approved drugs for prostate cancer. This “attack” circumvents many of the pathways that prostate cancer cells use to evoke drug resistance.

One of the biggest supporters of Jones’ work is Steven Dorfman, an engineer and leader in the aerospace industry who is now battling prostate cancer. Dorfman and his wife have personally contributed the majority of funds used so far in developing pyrvinium.

“It is a pleasure for me to be supporting such important research,” Dorfman said. “As I continue in my own fight against prostate cancer, I have become acutely aware for the need for new drugs for advanced disease.”

As a clinical researcher, I echo Dorfman’s sentiments. Prostate cancer still kills an estimated 27,500 men each year. This year, during Prostate Cancer Awareness Month, let’s celebrate the millions of prostate cancer survivors, but also focus on the many who face a more lethal form of the disease.

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Sumanta Kumar Pal, M.D., is an assistant clinical professor in the Department of Medical Oncology & Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope.

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Categories : Research

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