New space for discovery, collaboration: Discovery at the Brady has always thrived because surgeons and scientists have worked side by side — except in recent years, when the Institute expanded and space became too cramped. Now, thanks to the generosity of Maria and Andre Jakurski and the Peter Jay Sharp Foundation, collaboration thrives in a new, state-of-the-art, 12,000-square-foot facility. Located on the second floor of the Park Building, immediately adjacent to the Brady inpatient floor, the space is divided into modern laboratory facilities, faculty offices, and expanded workstations for staff.

Long before cyclist Lance Armstrong did what many considered impossible — winning the Tour de France race an unprecedented seven times — he did something equally remarkable, by beating devastating cancer that was well on its way to killing him. His amazing recovery has intrigued Hopkins scientists Donald S. Coffey, Ph.D., The Catherine Iola and J. Smith Michael Distinguished Professor of Urology, and Robert Getzenberg, Ph.D., for many years, and now it has inspired a whole new form of treatment.

Armstrong had very advanced testicular cancer — cancer so bad that it had spread throughout his body, including to his brain and liver. And yet, he was completely cured. “We had to know,” says Getzenberg, the Brady Research Director and the Donald S. Coffey Professor of Urology, “what makes testicular cancer so curable — even when it’s widespread? And how can we apply this to other solid cancers, like prostate cancer?”

Getzenberg and Coffey believed that they key to the “Lance Armstrong Effect” had to do with heat, and they called their idea “Temperature Enhanced Metastatic Therapy” (TEMT).
“The reason the testes are outside the rest of the body is that they exist at a much cooler temperature,” Getzenberg explains. If normal testicular cells move up into the body — into an atmosphere that, to them, is a sweltering 98.6 degrees — they stop functioning. “Our idea of why testicular cancers are so sensitive to therapy is that once they move from their cooler site, they are more vulnerable, and especially sensitive to heat.” Scientists already knew that raising
the temperature of cancer cells makes them much more susceptible to many kinds of treatment — chemotherapy, radiation therapy, and immunotherapy. Getzenberg and Coffey speculated that the heat somehow resulted in the structure of the cell’s nucleus becoming unstable. They figured that they could exploit this by warming — in a highly targeted way — the metastatic sites of a tumor, and then, once the cancer cells were vulnerable, blasting them with other treatments. “This new way of thinking about treating advanced cancer opens doors into new approaches that may help men with advanced prostate cancer.”

This TEMT approach has so much potential that, in a first-time ever project, Safeway Inc., the food and drug retailer, and the nonprofit Prostate Cancer Foundation have donated $6 million to fund a special program, called S.T.A.R. (for Special Team Amplification of Research), to explore the role of targeted heat and other strategies to treat prostate cancer. Led by Getzenberg, and including Hopkins colleagues Coffey and Theodore L. DeWeese, M.D., head of Radiation Oncology and Molecular Radiation Sciences, the program also puts together an interdisciplinary team of investigators from the University of Michigan Cancer Center and the University of British Columbia.

Safeway’s customers raised $3 million, in donations made at checkout. The Prostate Cancer Foundation (PCF) developed the collaborative research partnership and matched this money, dollar for dollar. The PCF will also bring in expertise from scientists at the University of Washington, from M.D. Anderson Cancer Center, and from Emory University. “Everyone who has input will be invited to the table,” says Jonathan Simons, M.D. — a Hopkins-trained oncologist and Brady alumnus — CEO and President and David H. Koch Chair of the PCF. “We are literally turning up the heat on metastatic prostate cancer.”

“We are pleased and honored to be associated with the S.T.A.R. Program initiative,” says Safeway’s Chairman, President, and CEO, Steve Burd, “and what promises to be pioneering work by some of the world’s top cancer researchers.”

Armstrong had very advanced testicular cancer. And yet, he was completely cured. How could this happen in prostate cancer?

The program’s goal, says Getzenberg, is to figure out the best way to use heat selectively
— aiming at the cancer cells only, but leaving adjacent healthy tissue unscathed. One way to do this may involve ultra-tiny “nanoparticles,” which are attracted to specific proteins on cancer cells. “Once the nanoparticle locates the specific protein, it can enter the cancer cell, heating it from the inside out after exposure to a magnetic field,” Getzenberg continues. “We are actively studying this and other mechanisms for targeted heat delivery to cancer cells. We need new approaches to cancer, and this one has great potential.”

EPCA-2 Update

In other news, Getzenberg and colleagues are moving “aggressively” on EPCA-2, a new biomarker we reported in the last issue of Discovery, working hard to make it available to men with prostate cancer, and to men who are being tested for it. This marker has proven
to be more sensitive than PSA, and a more specific test for prostate cancer. In early tests, it also performed better than PSA in showing which men had organ-confined cancer, and which men had cancer that had spread beyond the prostate. “One aspect of our work has been to increase its throughput,” says Getzenberg, so they can “run a large number of samples in a short period of time.” The scientists have conducted several clinical trials, including one in which they were able to correlate a man’s level of EPCA-2 with his likelihood of responding to radiation therapy. “We are also in the final stages of determining the most appropriate large commercial partner to develop the test for patients.” The EPCA-2 test is not yet available.