U-M and Karmanos receive NCI grant to find new solutions for prostate cancer

Michigan's two elite cancer programs are joining forces to find new solutions for prostate cancer. The University of Michigan Rogel Cancer and the Barbara Ann Karmanos Cancer Institute have received a prestigious $9.2 million grant from the National Cancer Institute.

The grant is through the NCI's SPORE, or Specialized Program of Research Excellence, which funds collaborative, interdisciplinary translational cancer research. The Michigan Prostate SPORE will focus on critical questions regarding how prostate cancer develops, with projects designed to address major barriers and challenges in diagnosis, treatment and metastasis.

The Rogel Cancer Center first received a prostate cancer SPORE grant in 1995, one of the first in the country. It has been continuously funded since then, resulting in several landmark discoveries that have identified key genetic drivers of prostate cancer.

In this renewal, the U-M team reached out to Karmanos researchers to leverage the two institutions' complementary strengths. U-M and Karmanos are the only two NCI-designated comprehensive cancer centers in Michigan.

With the Michigan Prostate SPORE, we hope to improve outcomes for men with prostate cancer by making scientific advances that address critical questions in how the disease develops and how best to treat it. The partnership between the Rogel Cancer Center and Karmanos will help us find innovative solutions that ultimately benefit patients."

Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, S.P. Hicks Professor of Pathology at Michigan Medicine and co-principal investigator

"We are honored to collaborate with U-M on this prestigious NCI SPORE grant to continue the Michigan Prostate SPORE," says co-principal investigator Elisabeth Heath, M.D., FACP, the Patricia C. and E. Jan Hartmann endowed chair for Prostate Cancer Research at Karmanos Cancer Institute, and professor of oncology and medicine at Wayne State University School of Medicine.

"We are fortunate that our research at Karmanos highlights our diverse population, which will complement the work underway at U-M. Collectively, we have the opportunity to gain a better understanding of metastatic prostate cancer in many populations and discover additional ways to treat this disease, as well as prevent it."

The Michigan Prostate SPORE is centered on three projects designed to translate laboratory discoveries into clinical advances. Projects range from early detection to tackling the most aggressive and advanced form of the disease, called castration-resistant metastatic prostate cancer.

1. Understanding a new subset of metastatic prostate cancer- Chinnaiyan's lab has previously found 7% of metastatic prostate cancer patients have loss of the gene CDK12. This subset of tumors was produced more immune T-cells and laboratory studies suggest they may be responsive to immunotherapy checkpoint inhibitors, a treatment that has overall had limited success in prostate cancer. This project will focus on metastatic castration-resistant prostate cancer with CDK12 mutation, seeking to uncover new treatment targets or biomarkers and to perform clinical trials using immune checkpoint inhibitors.
2. Using a urine test for early detection and high risk- One of the biggest questions in prostate cancer is distinguishing between which tumors are slow-growing, requiring minimal intervention, and which are likely to be aggressive and need immediate treatment. This project will investigate a new urine-based test developed at U-M that looks at a combination of multiple prostate markers, genes and other risk variants. The goal is to improve early detection of prostate cancer in those at high genetic risk and to understand among those diagnosed with prostate cancer who needs aggressive treatment and who may benefit from a less-intensive approach.
3. Overcoming treatment resistance- The hormone androgen plays a key role in prostate cancer, with current treatment including drugs designed to block signals from the androgen receptor. The problem is, nearly all tumors become resistant to these therapies. This project will investigate a new way of targeting the androgen receptor's messenger RNA in the hopes that disrupting the signaling upstream could block any androgen receptor signaling in the tumor, essentially depleting all androgen receptor signaling.

"Each of these projects will help us better understand the molecular mechanisms of prostate cancer progression and will also have a major clinical impact on the diagnosis and treatment of patients as we translate laboratory discoveries to the bedside," says co-principal investigator Ganesh Palapattu, M.D., Chair and George F. and Sandy G. Valassis Professor of Urology at Michigan Medicine.