A collaborative preclinical study between researchers at the Barbara Ann Karmanos Cancer Institute, Wayne State University (WSU), Beaumont Health, the National Institutes of Health, and Curemeta, LLC, has succeeded in finding a way to potentially suppress tumor growth for patients with prostate cancer. Their study, “Selective ablation of TRA-1-60+ pluripotent stem cells suppresses tumor growth of prostate cancer,” was published in March and will be included in Volume 13, Issue 7 of Theranostics (Impact Factor: 11.6).
“The study demonstrates that by using radiopharmaceutical therapy targeting the biomarker TRA-1-60, selective ablation of pluripotent cancer stem cells suppressed the progression of prostate cancer. We have also further shown that these TRA+ cells are culprits of tumor regrowth and require targeted treatment to prevent relapse and metastasis,” explained Nerissa Viola, Ph.D., leader of the Molecular Imaging Research Program at Karmanos, associate professor at WSU School of Medicine, and co-author of the study.
The team explored how targeting TRA-1-60+ (TRA) can be used clinically for prostate cancer. They used an antibody specific to TRA, radiolabeled with zirconium-89, an isotope that is used for positron emission tomography (PET) imaging to detect these cells within the prostate tumors. After detection, they substituted the isotope with Lutetium-177, an isotope that emits beta particles that causes single and double-strand DNA breaks. The team injected this drug in mice with prostate cancer cells following the guidelines established by Wayne State University’s Institutional Animal Care and Use Committee. They then subsequently looked at tumor growth delay over time.
“Preclinical studies using rodents, such as mice, allow us to test the efficacy of drugs like TRA-targeted RPT (radiopharmaceutical therapy). Once we validate and confirm the potency of the drugs, we can move forward to clinical trials in prostate cancer patients,” said Dr. Viola.
From the experiments, researchers came to three conclusions: there is a clinical significance of TRA expression in prostate cancer, engineered and tested radiotheranostic agents can image and treat TRA+ prostate cancer stem cells, and the ablation of the TRA+ cancer stem cells did suppress the growth of prostate cancer. Their findings lead to the potential of future studies.
“The next step would be to look at targeted drug combinations with TRA RPT that will not only suppress growth but completely eradicate the tumor and prevent relapse,” concluded Dr. Viola.
Jordan White, Ph.D., a graduate of the Cancer Biology Program at WSU School of Medicine and a mentee of Dr. Viola, is the study’s lead author. Additional co-authors include Karmanos Molecular Therapeutics Research Program members and professors at WSU School of Medicine Steve Patrick, Ph.D., Seongho Kim, Ph.D., and Elisabeth Heath, M.D., FACP, medical oncologist, member of the Tumor Biology and Microenvironment Research Program, leader of the Genitourinary Oncology Multidisciplinary Team (MDT), member of the Phase 1 Clinical Trials MDT, associate director of Translational Sciences, and the Hartmann Endowed Chair for Prostate Cancer Research at Karmanos.
Nicholas Ramos and Allen-Dexter Saliganan were both research assistants with Dr. Viola at the time and they contributed to the study. Jacob Lindquist, graduate student research assistant in the Cancer Biology Program at WSU; Kayla Conner, Ph.D., a graduate of the Cancer Biology Program; Wendy Wiesend, M.D., Beaumont Health System; Michael Schopperle, Curemeta, LLC; and Joon-Yong Chung, Ph.D., Meghan Bell and Freddy Escorcia, M.D., Ph.D., from the National Cancer Institute and the National Institutes of Health are also co-authors of the study.
The research team would like to acknowledge the WSU Cancer Biology Program for supporting the three graduate students who worked on the project, including the DeRoy Testamentary Foundation Fellowship.
Read the study here.