Newswise — The Prostate Cancer Foundation (PCF) has awarded a $1 million grant to a renowned specialist at the University of Chicago Medicine Comprehensive Cancer Center.

Physician-scientist Akash Patnaik, MD, PhD, MMSc, and his team, recipients of the 2022 Michael & Lori Milken Family Foundation-PCF Challenge Award, will investigate developmental immuno-oncology and hormonal therapies in advanced prostate cancer. As an expert in cancer biology and a translational physician-scientist, Patnaik is an authority on prostate cancer treatment.

PCF Challenge Awards are granted to select teams at leading cancer research centers, following a rigorous two-tier peer review process. They fund international, multi-institutional, cross-disciplinary teams of investigators conducting highly innovative and transformative research with the greatest potential for accelerating new and improved treatments for advanced prostate cancer.

Immune checkpoint immunotherapies are cancer treatments that have been highly effective in several cancer types and can result in long-term regressions and cures. However, these treatments have yet to demonstrate significant success in prostate cancer.

A major reason for immunotherapy failure in advanced prostate cancer is the “immune desert” tumor microenvironment, which is infiltrated with cancer-promoting myeloid cells, particularly macrophages. Therapeutic strategies to reprogram these tumor-promoting macrophages may sensitize prostate cancers to immune-based medicines.

Patnaik and colleagues made a seminal discovery that NLRP3, an immune-activating protein, is specifically expressed in tumor-promoting macrophages following FDA-approved androgen deprivation therapy (ADT) commonly used for treatment of advanced prostate cancer.

They found that NLRP3 activation promoted tumor clearance in combination with ADT in a preclinical mouse model of prostate cancer.

In this newly funded project, a multi-institutional team led by Patnaik will investigate whether activation of NLRP3 will overcome immunosuppression and sensitize advanced prostate cancer to immune checkpoint immunotherapy.

“This award will support our exciting laboratory bench-to-bedside studies on NLRP3 as a novel innate immunotherapeutic target in prostate cancer,” said Patnaik.

The team will demonstrate the mechanisms and potential for NLRP3 activation as a new treatment strategy, alone or in combination with immunotherapy and/or androgen deprivation therapy. If successful, this project will pave the way for NLRP3-activation-based immuno-oncology combinations for advanced prostate cancer treatment.

“We are optimistic that this strategy will lead to definitive medicines to alleviate suffering and improve survival for our patients with advanced prostate cancer,” Patnaik said.

“Congratulations to Dr. Patnaik and his co-investigators at Oregon Health & Science University and Massachusetts General Hospital on their 2022 PCF Challenge Award,” said Howard R. Soule, PhD, executive vice president and chief science officer for the Prostate Cancer Foundation. “We are proud to invest in the work of these gifted physician-scientists because we know their discoveries will move us closer to our common goal of eradicating prostate cancer and ending the death and suffering caused by this disease.”