Current treatments for prostate cancer make it possible to cure the deadly disease when caught early, but in about one-third of the cases resistance or lack of response to the drugs can allow the cancer to spread out of control – and doctors don’t know exactly why.
A UCSF-led team was awarded $10 million over three years last week to figure that out and come up with better treatments as well as ways to use new and existing therapy combinations in more targeted, personalized ways.
“The success in improving early care is a wonderful story, but the problem is 28,000 men still die of advanced disease every year in the United States,” said Dr. Jonathan Simons, chief executive officer of the Prostate Cancer Foundation, which funded the award along with Stand Up to Cancer, a charitable project established by media, entertainment and philanthropic leaders to raise awareness and money for cancer research.
More than 2 million men in the United States have been diagnosed with prostate cancer, the most common non-skin malignancy in men.
In about a third of prostate cancer cases, patients require no treatment other than monitoring, because the cancer is slow growing and has not spread. In another third of cases, patients are treated and cured. But for the remaining patients, the cancer recurs after treatment and can spread to the bones, lymph nodes or other parts of the body.
Because the cancer is fueled by the hormone testosterone, the disease is commonly treated with testosterone-blocking hormone therapies. But even so, the cancer cells can develop the ability to make their own hormone and learn to survive, giving the disease the ability to progress.
Doctors are getting new weapons to fight back against advanced cases. The U.S. Food and Drug Administration recently approved a surge of prostate cancer drugs, some of which are designed to address the problem of resistance.
These include Johnson Johnson’s Zytiga, which was developed at UCSF, and a drug called Xtandi. Both use a similar mechanism that allows the drug to go inside the cancer cell and block it from making its own testosterone.
But they still aren’t effective for all patients.
“We’re already seeing resistance to these agents,” Dr. Eric Small, deputy director of UCSF’s Helen Diller Family Comprehensive Cancer Center and principal investigator of the project. “The outcomes are fairly predictable and bad. Our patients die.”
Even those who do well will eventually develop resistance because the cancer cells adapt and learn how to survive on even a tiny bit of residual testosterone, Small said. Some patients simply don’t respond at all.
Either way, there’s no way for doctors to know how a patient will respond until the resistance occurs.
“We don’t know who these patients are or why or how to treat them,” Small said.
Small is the leader of the “dream team,” which beat out 13 other competitors for the $10 million award. The team, selected by the nonprofit American Association for Cancer Research, involves more than 30 investigators at six West Coast institutions: UCSF, UCLA, UC Davis, UC Santa Cruz, the Oregon Health Sciences University and the University of British Columbia.
The team will focus on identifying the pathways the cancer cells use to work around the current therapies and figure out ways to inhibit them using a combination of treatments to reach those escape routes in multiple ways.
Last week in separate but related research, scientists from the East Coast and the United Kingdom announced in two studies that they had identified separate “signatures” for prostate cancer that could better determine the aggressiveness of the disease and could be used to predict survival. The studies were published in the journal the Lancet Oncology.
“The problem is these signatures tell you you have high-risk cancer, but they don’t tell you why and they don’t tell you what to do with it,” Small said. “What we’re going after is fundamentally different: try to understand the pathways that are involved in developing resistance and using co-targeting agents to treat it.”
The team will take biopsies and blood samples from about 500 patients with advanced prostate cancer. The samples will undergo a comprehensive molecular assessment and an analysis to determine the activity levels of the known and novel pathways.
Knowing the pathways should give researchers the targets on which to test new drug combinations, and that approach is expected to lead to treatments tailored to each patient’s disease. “It really does get at this personalized approach to an individual patient based on the characteristics of his cancer,” Small said.
Social media tool
A key component of the team’s project is the development by engineering experts at UC Santa Cruz of a new social media tool called MedBook to connect researchers, doctors and patients in a shared platform. The idea is to promote collaboration and speed the process of figuring out which cocktail of prostate cancer drugs work best for which patients.
“Scientific researchers may have their own very special program to do data analysis, but they don’t have a way to share that around,” said Ted Goldstein, a former Apple executive who developed MedBook and is completing his doctorate in biomolecular engineering at UCSC.
Goldstein, who describes MedBook as a “Facebook for cancer,” said the application could ultimately be used for other cancers and more directly involve patients.
The Prostate Cancer Foundation’s Simons described the team as exceptionally information-savvy and “enabled by the spirit and culture of Silicon Valley.” But he said the real draw is the hope of developing results quickly.
“It has a very high probability of helping prostate cancer patients who are fighting the disease right now. That’s what makes it special,” Simons said. “It’s all about the speed of delivering the right drug to the right patient.”
Major killer of men often recurs
Prostate cancer is the most common non-skin cancer in the United States, affecting 1 in 6 men.
– While early detection has greatly reduced the death rate, prostate cancer is still the second-leading cause of cancer deaths in men after lung cancer.
– In about a third of prostate cancer patients, the disease recurs, becomes resistant to treatment, and spreads to other parts of the body.
– The five-year survival rate for men with cancer that has not spread outside the prostate or has just spread to nearby areas is almost 100 percent. But in patients whose cancer has spread to distant nodes or organs, the rate drops to 29 percent.
Sources: UCSF, Prostate Cancer Foundation, American Cancer Society
Victoria Colliver is a San Francisco Chronicle staff writer. E-mail: firstname.lastname@example.org