Lange-Vessella partnership that became IPCR lured to Seattle 25 years ago

It's been a quarter century since the unusual team of an academic prof and a medical doctor was lured to Seattle to launch what would became the Institute for Prostate Cancer Research (IPCR), where a world-class team and leading-edge initiatives have made Seattle a nexus for prostate cancer research and care.

Paul Lange, M.D. and Robert Vessella, PhD, had already been a team at the University of Minnesota for a dozen years when they decided in 1989 to accept an offer to come to the University of Washington to launch the collaborative effort that a few years later would officially become IPCR. By then it would be a collaboration between University of Washington Medical Center and the Fred Hutchinson Cancer Research Center.

Paul Lange, M.D.

In a sense, Lange and Vessella were medical opportunists in deciding to focus on a cancer for which they thought "there might be a light at the end of the tunnel," despite the fact that at that point there was basically no funding available for prostate-cancer research. "No one really cared at the time about an old man's disease," Lange recalled.

Appropriately but coincidentally, the 25^th anniversary of the Lange-Vessella partnership in Seattle comes as IPCR is in the midst of a $20 million fund-raising campaign aimed at creating an innovative program for individualized treatment of prostate-cancer sufferers around the state.

Plus it was recently announced that IPCR will be part of a team of prestigious institutions to participate in a $10 million grant from the Stand Up to Cancer program, which is supported by the American Association of Cancer Research and the Prostate Cancer Foundation.

Robert Vessella, Ph.D

IPCR will be partnering with Harvard, University of Michigan, Sloan Kettering and London University, names that indicate the role that IPCR has come to play in prostate-cancer research around the world.

The image that has developed since the UWMC and The Hutch collaboration became formal as IPCR in about 2000 is such that there's a growing sense that it could well be the place where a cure for the disease, now certainly when rather than if, comes about.

IPCR ranks third in the country for federal funding, with about $10 million in 2012, and is in the top five in prostate-cancer funding, Lange says. Over the years, he estimates, at least $60 million, mostly from NIH, has come to IPCR, a number made more impressive by the fact it doesn't include the 50 percent "institutional overhead" that UW takes from the original grant amount. The Hutch takes 60 percent.

But ironically, IPCR has dramatically lagged in raising the private funds that the NIH views as a key to its own funding decisions.

"We are significantly behind the eight to 10 prostate-cancer research institutions in the country in keeping up with private fund raising, which is essential if we are to retain a world-class team and explore new ideas that need to be developed because they are not yet primetime enough for the NIH to fund," says Lange.

Thus the importance of the fund-raising campaign now under way called ACT-SMART, which seeks to raise $20 million over five years from private sources to create relationships with a dozen or more medical facilities around the state in developing individualized treatment programs for residents of various communities.

The goal of ACT-SMART is to sequence the whole genome of patients and their prostate cancers, focus on the most important abnormal genes in the cancer and then devise a targeted individualized treatment program, then patients are sent home to have their individualized treatment carried out in their hometown medical facility.

"We are going to use genomic medicine to determine what the patient's genes show, then develop targeted therapies aimed at the specific cancer," Lange said, noting that eventually the program will be extended to Oregon, then Idaho and Montana.

A couple of developments in the early '90s assured IPCR's emergence as a world-class institute in the field of prostate-cancer research and cemented a pre-eminent role for Lange and Vessella as globally recognized leaders in the quest for answers to prostate cancer.

One of those developments came in 1992 with an innovation called "rapid autopsies" that has attracted the attention of researchers both nationally and internationally as well as pharmaceutical companies. It's a process in which cancer tissue that has metastasized is removed from the bodies of a deceased prostate-cancer victims with the same speed and precision as organs are removed for transplant.

The roughly 100 such autopsies that Lange's team has performed since the process was pioneered at IPCR, and which are conducted at only one other institution in the county, allow harvested cancer cells to be implanted in mice. Lange says about 15 percent of the implants take, becoming what are referred to thereafter as "tumor avatars," and producing thousands of samples.

Another key development in 1992 was a partnership that emerged with Leroy Hood, who had recently arrived at the University of Washington, with funding from Bill Gates Jr, to found and chair the Molecular Biotechnology Department.

Hood, already internationally prominent as developer of the automated DNA sequencer that was the key to the human genome project, recalled in an interview how he and Lange, both heading departments at UW, got together at a retreat to discuss how genomics could be applied to prostate-cancer research.

"We decided to work together and I outlined on a napkin at dinner a genomic approach to prostate-cancer research," Hood recalls. "Then Paul and I agreed to help Michael Milkin, as he created a series of seminal meetings on the genomic approach to prostate cancer."

"Lee was hugely instrumental in putting us in the national spotlight," Lange said. "Thanks to a variety of influences, Lee decided to devote a large part of his translational research efforts to prostate cancer. The support of the Michael Milkin organization to the tune of about $12 million over the years was largely due to the participation of Lee and his group in our research efforts."

Hood continued to work with Lange and Vessella until he left UW in 2000 to found the Institute for Systems medicine, which he still heads.

It was in 1993 that Lange and Vessella began discussing with researchers at The Hutch the idea of teaming to form an institute. And that was also the year that the first grant, from the NIH O'Brien Center, was received, for $2.8 million in direct costs over a five-year period, at the end of which it was renewed again for another five years.

Lange routinely ascribes human characteristics to the cancer he seeks to conquer, possibly viewing the opponent whose ways occupy much of his attention as a worthy foe. Thus he characterizes the PSA test, which he helped gain approval for in testimony on its benefits before the FDA on several occasions in the early '90, as "allowing us to know what the cancer is thinking."

And in explaining to a listener that the prostate cancer his team deprived of the testosterone it needed to survive soon began a comeback, Lange's voice rises to exclaim: "It learned to live without it!" Then he continues to explain, replaying the excited frustration he likely felt at the time, as further research determined "no, it learned to make its own testosterone! Like the cancer said 'hey guys, we're going to get really sick if we don't do something about this!.'"

But that finding was a research victory because it indicated that the understanding that cancer needed testosterone to survive was accurate.

Perhaps by attributing those human characteristics to his foe, the victory over prostate cancer, when it comes, will feel more personal and thus more satisfying for Lange, whose personal battle included his having to undergo surgery for his own prostate cancer a few years ago.