Binghamton team to develop new cancer therapy
By Anna-Tan Wilson, interim department chair in Biological Sciences
The American Urological Association recently issued a Best Practices Statement which recommends cryosurgery of the prostate as both a primary and salvage therapy for patients with prostate cancer. A team of faculty members, alumni and graduate students at the Department of Biological Sciences at Binghamton University, working with physicians at Pittsburgh’s Allegheny General Hospital, pioneered the technology and surgical methods. It required significant effort to develop cryosurgery, a long-established therapy in dermatology and gynecology, as a primary treatment option for prostate cancer.
According to Dr. John G. Baust, UNESCO Chair and Professor of Biological Sciences and project leader at Binghamton, “When we began this partnership in the early 1990s to develop a new minimally-invasive treatment for cancer, we initially underestimated the challenges that our team would face. It was well-recognized that tissue freezing could be extremely effective in killing cancer, but the issue of physician control of the process became critical.”
The Binghamton team of faculty and graduate students assumed responsibility for developing the surgical device necessary to precisely apply the freezing temperatures to the prostate while the physician was able to observe the destruction of the cancerous target with the aid of ultrasound during the actual surgery. The Allegheny General team developed the surgical protocols and managed the patients during the years that followed treatment to assure a successful outcome. Both teams partnered to teach this new therapy to many thousands of urologic surgeons and interventional radiologists at many of the major medical universities in the U.S. and Europe.
The Binghamton team was also challenged to work out the “biology of the disease” and its responses to freezing. Dr. Robert Van Buskirk, professor of Biological Sciences and Bioengineering, led a very extensive study that delved into to the molecular biology of prostate cancer and low temperature responses. “One of the most essential groups of contributors that led to the success of this effort has been our extremely strong team of graduate students,” he said.
William Hollister PhD '03, biology faculty member at Broome Community College, made a critical discovery identifying a previously unrecognized form of cell death following freezing known as “apoptosis” in a population of dying cancer cells.
“This was a key that opened the door,” said John M. Baust, PhD '01, president of Cell Preservation Services in Owego, N.Y. “We now had a path to both better understand how the freezing process killed prostate cancer but also how we might improve the efficiency of the death process during treatment.” Baust meticulously analyzed the timing of the molecular events that led to a cell's demise following freezing. “By understanding the sequence of events that often leads to cancer cell death, we were then able to have other researchers add secondary agents to further stress the cells so that we could assure the complete destruction of the cancer,” he said.
One important unknown needed to be addressed to assure broad-based acceptance within the medical community. The Binghamton team needed to understand and explain why some forms of prostate cancer respond differently to treatment. It has been long recognized that there are many forms of what is generically referred to as “prostate cancer,” and these various forms respond differently to radiation, chemotherapy and even a freezing insult.
Daniel Klossner, PhD '07, faculty member at SUNY Delhi, provided a critical answer by discovering that the presence or absence of a specific protein known as the “androgen receptor” correlates with the relative “hardiness” of the prostate cancer. The protein is found in easy-to-kill cancers while “old cancers,” which lack the protein, present greater curative challenges. This discovery helped lead to the adoption of a set of standard treatment parameters. These findings may contribute to a change in how hormonal therapy is used in prostate cancer patients as the application of anti-androgen therapy often results in the emergence of more difficult-to-treat prostate cancers.
Graduate student Anthony Robilotto is building on this foundation and working to develop the scientific basis for yet the next improvements. Robilotto has developed tissue engineered human “prostates” that contain different genetic variants of the cancer and attempts to “cure” the cancers with innovative combinations of low temperature and chemotherapeutic agents.
While this team’s cancer research continues, the critical results of their 10 years of patient treatment were recently published in the Journal of Urology. This landmark study demonstrated that 77 percent of patients treated at Allegheny General were cancer-free based on biopsy data.
“This is a remarkable number, and importantly, this success is being matched at numerous other community hospitals and leading medical centers with their five-, seven- and 10-year studies,” Baust said. To date, more than 40,000 prostate cancer patients have been treated with this therapy and the improved devices that have evolved.
The success of this project is now leading directly to its expansion into other problematic cancers. Kristi Snyder, PhD '04, now director of operations and principal scientist at Cell Preservation Services, Inc., is moving this technology in new directions. Snyder is collaborating with graduate students Will Corwin and Kim Berdine to bring this life-saving technology into patients with breast, kidney and lung cancer.
“The prospects for expanding the application of cryosurgery to other focal tumors is absolutely exciting," Snyder said. "Think of it! This is a therapeutic procedure that is applied in just a few minutes without traditional, invasive surgery, without the complicating co-morbidities common to radiation and chemotherapy, is relatively pain-free, is bloodless, and in the case of prostate cancer treatments, patients go home the same or next day. We need to move and are moving aggressively to expand this next generation therapy.”