The University of Michigan Rogel Cancer Center in Ann Arbor and the Barbara Ann Karmanos Cancer Institute in Detroit have received a $9.2 million grant from the National Cancer Institute to study prostate cancer.
The grant is through the institute’s SPORE, or Specialized Program of Research Excellence, which funds collaborative, interdisciplinary translational cancer research. The Michigan Prostate SPORE will study how prostate cancer develops and includes projects designed to address challenges in diagnosis, treatment, and metastasis, or the development of secondary malignant tumors at a distance from the primary cancer site.
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 discoveries that have identified key genetic drivers of prostate cancer.
“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,” says Dr. Arul M. Chinnaiyan, director of the Michigan Center for Translational Pathology, S.P. Hicks professor of pathology at Michigan Medicine, and co-principal investigator. “The partnership between the Rogel Cancer Center and Karmanos will help us find innovative solutions that ultimately benefit patients.”
In this renewal, the U-M team reached out to Karmanos researchers to help. The institutions are the only ones in Michigan that are National Cancer Institute-designated comprehensive cancer centers.
“We are honored to collaborate with U-M on this prestigious NCI SPORE grant to continue the Michigan Prostate SPORE,” says co-principal investigator Dr. 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.
The first project aims to understand a subset of metastatic prostate cancer. Chinnaiyan’s lab previously found 7 percent of metastatic prostate cancer patients have loss of the gene CDK12. This subset of tumors produced more T-cells, and laboratory studies suggest they may be responsive to immunotherapy checkpoint inhibitors, a treatment that has had limited success in prostate cancer. The project will focus on metastatic castration-resistant prostate cancer with CDK12 mutation, seeking to uncover new treatment targets or biomarkers to perform clinical trials using immune checkpoint inhibitors.
The second project will focus on developing a urine test for early detection and risk detection. It is difficult to distinguish which prostate cancer tumors are slow-growing, requiring minimal intervention, and which are likely to be aggressive and need immediate treatment. The project will investigate a test developed at U-M that looks at a combination of prostate markers, genes, and other risk variants.
The third project will study the hormone androgen and overcoming treatment resistance. The hormone 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 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 Dr. Ganesh Palapattu, chair and George F. and Sandy G. Valassis professor of urology at Michigan Medicine.