A five-year, $12.5 million grant has been awarded to researchers at UW–Madison to investigate metastatic, or advanced stage, prostate cancer, the second most common cause of cancer death in men.
Dr. Joshua Lang, principal investigator and professor of medicine at the University of Wisconsin School of Medicine and Public Health, leads this P01 grant which involves a number of other independent investigators, leveraging institutional strengths at UW–Madison, the University of California San Francisco and the University of Washington.
Prostate cancer is increasing in men, according to the National Cancer Society. The initial treatments of prostate cancer focus on hormone therapies, which lower or block testosterone, as most prostate cancers require testosterone to grow and spread. However, prostate cancers often become resistant to hormone treatment. When the cancer has spread to other parts of the body besides the prostate, it is referred to as metastatic.
A Research Program Project Grant, called a P01 grant, is a type of National Institutes of Health funding award that supports multiple teams, often at several universities, whose individual projects hold merit. By working together, the groups can accelerate scientific discovery.
In this Q&A, Lang explains the project’s goals and challenges, as well as UW’s innovative cancer modeling technique that will play a critical role.
What problems are the collaborative teams working to solve?
The goal of this P01 is to understand how prostate cancer cells develop resistance, develop new blood tests to identify that resistance and find new therapies to help men live longer with prostate cancer. There has been a dramatic increase in the percentage of men presenting with metastatic prostate cancer, especially in the state of Wisconsin, which ranks 41st in the country for prostate cancer survival. Those rates are worse when we look at Black men and men of Hispanic descent, with mortality rates two to six times higher than other men. While the therapies we use to treat prostate cancer are initially very effective, none are curative, and the lifelong hormone therapies have significant impacts on quality of life.
Why are prostate cancer rates rising?
Access to health care in rural parts of the state plays a significant role. A family history of cancer including prostate, breast and pancreas cancer is also associated with [cancer risk]. The lack of prostate cancer screening plays a significant role. There are also gaps in treatment: over half of men don’t get the right combination of therapies and don’t get the right genetic testing done. Men are just not getting the best care and if we did a better job of delivering that care, that would also have a significant impact.
Describe the three individual projects underway at participating universities.
Project 1, which is based here at UW–Madison, is focused on understanding how prostate cancers become resistant to hormone therapies but still use the androgen receptor, which binds with testosterone, to grow and spread to bone. Project 2, based at the University of Washington focuses on prostate cancers where the androgen receptor doesn’t function, and cancer often spreads to the liver. We still don’t understand what makes those cancers tick, let alone how to treat them. Those are the prostate cancers that can become lethal within six to 18 months. Project 3, based at the University of California San Francisco studies prostate cancers that lose androgen receptor function and can actually transform into a different type of prostate cancer called neuroendocrine prostate cancer. That’s another extremely aggressive cancer that can become lethal in six months or less.
Across all those projects, we’re trying to figure out why and how prostate cancer diverges from one type to another, and where we can intervene earlier to prevent the cancer from becoming so aggressive.
How are the three universities working together?
This grant supports a team of world-class investigators who are leaders in their respective fields. In Wisconsin, we have experts in translational research techniques (bringing medicine “bench to bedside”). At University of California San Francisco, they have world leaders in novel clinical trials and in functional genomics, which are cutting-edge tools to describe gene function and behavior. The University of Washington similarly has clinical trials and animal models, but they also have the world’s largest rapid autopsy program. This is when patients make this incredible donation — men who are dying of prostate cancer donate their bodies to research. We don’t have something like that at UW. The rapid autopsy program allows study of cancer that has spread to different parts of the body.
What inspired you to study metastatic prostate cancer?
I had one patient ask me a simple question when we were talking about different therapies. He asked, “Josh, why did my cancer stop responding to the treatment that had been working for more than a year?” I didn’t have an answer for it. Then he said, “You’ve offered two different treatments. Why do you think one will work versus the other?” And I still didn’t have an answer. There were no genetic tests or scans that we could do to help guide us to the best option for his specific cancer. This patient, and so many others, are the inspiration behind the research in my laboratory and our collaborations, and this grant is going to allow us to dramatically accelerate all our efforts.
What are the side effects of current prostate cancer therapies?
Hormone-based therapies bring testosterone almost to zero, which has huge impacts on quality of life: significant fatigue, muscle weakness and osteoporosis (bone density loss). There’s also increased risk of heart disease, high blood pressure, cholesterol and diabetes — it’s a really long list of side effects. Some of these hormone therapies cause side effects similar to menopause such as fatigue, hot flashes, depression and mood changes.
Describe your work on UW’s innovative cancer modeling technique known as “tumor-on-a-chip.”
Cancer models are critical to testing different therapies, because they help us understand not only how cells interact to lead to the development of cancer, but also how the body develops resistance to treatment. Historically we’ve used animal models and cell culture, but the problem is human prostate cancer is very different than what we observe in mice, especially in different organs such liver or bone. We’re now creating human tumors-on-a-chip with our close collaborators in biomedical engineering, Dr. David Beebe and Dr. Sheena Kerr. We use cells from patients to recreate their tumors on microfluidic chips with different types of bone cells or liver cells. We think that these models will help us uncover why different prostate cancers spread to different parts of the body and become lethal. This would allow us to then treat those chips with different drugs to see which one’s most effective, depending on where the cancer has metastasized.
Is it challenging to work on a group project with far-flung colleagues?
The biggest challenges with these large collaborations across universities are aligning interests, resources and our individual strengths to achieve a larger goal. We have been working with these collaborators for more than four years and this synergy has allowed us to move forward light years faster than we would have otherwise. Now we get to move forward with an opportunity to revolutionize how we care for men fighting prostate cancer. And we hope that these lessons will be applicable to every cancer because these are really fundamental biological questions.
Besides you, who else is making this research possible?
We have exceptional teams at every university, from the scientists and researchers in the lab, to the clinical trial staff, to our bioinformatics and computational team. The most important participants are our patients who teach us what we should study about their cancer. These fearless patients also donate samples for research, all to help others who will fight this disease in the future. They’re the heart of what we’re trying to do.
– Author Mary Bosch is a 2025–26 science communications intern at the School of Medicine and Public Health
The work was funded by National Institutes of Health grant P01 CA298991.
