The Sidney Kimmel Cancer Center and Brady Urological Institute have received a prestigious five-year SPORE (Specialized Programs of Research Excellence) grant from the National Cancer Institute, totaling over $11 million. 

“This is the largest program grant centered around one disease that anyone can get,” says Mohammad Allaf, M.D. “Only eight of these grants are awarded across the entire country,” placing Johns Hopkins among a select few institutions nationwide recognized for their innovative work in prostate cancer research. 

This is not the Brady’s first SPORE grant, Allaf notes. But “this recognition of our efforts in prostate cancer while we are also building our strengths in other urologic diseases, is a badge of honor for our urologists, medical oncologists, radiation oncologists, and basic scientists.” 

Under the leadership of medical oncologist Samuel Denmeade, M.D., the R. Dales Hughes Professor of Oncology and Director of the Johns Hopkins Division of Genitourinary Oncology, and scientist Shawn Lupold, M.D., the Prostate SPORE Program aims to turn laboratory discoveries into new treatments to help men fighting advanced prostate cancer. The research will tackle the complex ways in which prostate cancer cells evade treatment, focusing on factors that contribute to metastasis and treatment resistance. The SPORE projects include the list below.

Expanding Bipolar Androgen Therapy (BAT)

This project is led by Denmeade and pathologist Angelo M. De Marzo, M.D., Ph.D. Testosterone is a major driver of prostate cancer, and standard hormonal therapy attacks cancer by shutting down male hormones.“But prostate cancer can get used to this environment,” says Denmeade, “and can learn to grow in the absence of male hormones. BAT shakes up the cancer. It alternates shutting down male hormones with slamming the body with high doses of testosterone, making cancer more vulnerable to treatment.” 

When Denmeade and medical oncologist Mark Markowski, M.D., Ph.D., explored this idea several years ago, people thought they were – well, batty. “This Hopkins-initiated, novel treatment seemed controversial at first,” says Allaf. “But initial funding from the Patrick C. Walsh Prostate Cancer Research Fund, which supports high-risk, high-reward ideas, helped the team gather promising data that led to larger studies,” showing that BAT can be safe and effective, leading to improvements in patients’ quality of life. 

In this project, researchers will combine the one-two punch of BAT with a third weapon: a drug called ZEN-3694, which targets a protein that helps cancer cells grow. They also will analyze patients’ tumor samples “to help us understand which individuals respond best to the treatment,” Denmeade says. 

Helping the Body Fight Cancer

This project is led by medical oncologists Eugene Shenderov, M.D., Ph.D., Drew Pardoll, M.D., Ph.D., and Ken Pienta, M.D. “The goal,” says Lupold, “is to boost the immune system to fight prostate cancer by targeting B7-H3,” a protein produced in higher amounts by aggressive prostate cancer cells. The team will investigate two experimental treatments: a highly precise antibody drug conjugate that delivers a cancer-fighting agent directly to the tumor, and a monoclonal antibody drug enoblituzumab, which boosts the immune response against cancer. 

Expanding the use of PARP Inhibitors

PARP inhibitor drugs such as olaparib can be effective in prostate cancer – but only in patients who have specific gene mutations related to DNA repair. In this project, led by oncologists Vasan Yegnasubramanian, M.D., Ph.D., and Michael Carducci, M.D., investigators will combine olaparib with decitabine, which protects DNA from certain cancer-caused changes. “We would like to expand the use of PARP inhibitors to a wider group of patients,” says Denmeade. The team hopes “the combination of decitabine with olaparib will create a “triple threat” against cancer by damaging its DNA, activating the immune system against the tumor, and reducing the activity of cancer-promoting signals.” The investigators will evaluate this drug combination in a clinical setting through the ongoing PARENT (PARP Inhibitor plus Epigenetic Therapy) trial.