A Wayne State University School of Medicine physician-researcher will co-lead a $9.2 million effort backed by the National Cancer Institute to find new solutions to combat prostate cancer.

Elisabeth Heath, M.D., FACP, professor of Oncology and of Internal Medicine at the Wayne State University School of

Medicine, serves as co-principal investigator of the grant, which was awarded to Wayne State University and the University of Michigan Rogel Cancer Center.

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 of the grant, U-M reached out to WSU researchers to leverage the two institutions’ complementary strengths. U-M and WSU are the only two NCI-designated comprehensive cancer centers in Michigan.

“We are honored to collaborate with U-M on this prestigious NCI SPORE grant to continue the Michigan Prostate SPORE,” said Dr. Heath, the Patricia C. and E. Jan Hartmann Endowed Chair for Prostate Cancer Research at the Barbara Ann Karmanos Cancer Institute. “We are fortunate that our research 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.”

“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 ... will help us find innovative solutions that ultimately benefit patients,” said co-principal investigator Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at Michigan Medicine.

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.

• Understanding a new subset of metastatic prostate cancer. Dr. Chinnaiyan’s lab has previously found 7% of metastatic prostate cancer patients have loss of the gene CDK12. This subset of tumors 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.
   
• 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 less-intensive approaches.
   
• 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. However, 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 hope that disrupting the signaling upstream could block any androgen receptor signaling in the tumor, essentially depleting all androgen receptor signaling.

This project is funded through National Cancer Institute grant P50CA186786-06.