— Award will accelerate UK team's work to extend survival for men with advanced prostate cancer —

The Prostate Cancer Foundation (PCF) today announced a $10 million unrestricted gift from an anonymous donor to launch a TACTICAL (Therapy ACceleration To Intercept CAncer Lethality) Award, which will address a critical challenge in advanced prostate cancer: understanding and overcoming resistance to the targeted radioligand therapy ¹⁷⁷Lu-PSMA-617 (Pluvicto^®).

The Prostate Cancer Foundation strategically manages large gifts to accelerate scientific breakthroughs that have improved care and extended the lives of tens of thousands of patients. The new three-year award will support a prestigious team of investigators led by Professor Nick James of The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, along with Professor Gerhardt Attard of University College London and Dr. Hoda Abdel-Aty of The Royal Marsden NHS Foundation Trust. The researchers will analyze tissue samples and imaging data from patients enrolled in STAMPEDE2, a clinical trial testing new therapies in patients with advanced prostate cancer. Their goal is to identify biomarkers that predict which patients will respond to ¹⁷⁷Lu-PSMA-617 (Pluvicto^®), uncover mechanisms of treatment resistance, and discover new therapeutic targets.

Prostate cancer affects one in eight men in the United States and UK. It is the most common cancer for men in 118 countries and the leading cause of death among men in 52 countries. Prostate cancer is an urgent health issue worldwide, with an estimated 397,000 deaths each year. While new therapies have helped many patients live longer, nearly all men with advanced disease eventually stop responding to treatment. Understanding why this occurs and how to overcome it remains a critical challenge.

¹⁷⁷Lu-PSMA-617 targets a protein called PSMA that is abundant in prostate cancer cells, delivering radiation directly to tumors while sparing healthy tissue. The therapy is currently approved for metastatic castration-resistant prostate cancer and is being tested in earlier stages of advanced disease through trials like STAMPEDE2. Building on this work, Dr. James and his colleagues will perform targeted biopsies of cancer lesions that are resistant to ¹⁷⁷Lu-PSMA-617 to identify mechanisms of resistance, biomarkers of response and resistance, and new treatment targets.

"This team will address critical questions for patients with advanced prostate cancer: which patients will benefit most from ¹⁷⁷Lu-PSMA-617 and what biological mechanisms allow some tumors to evade this targeted therapy," said Andrea K. Miyahira, PhD, Vice President of Global Research and Innovation at the Prostate Cancer Foundation. "Dr. James and his team's findings could transform treatment selection and help doctors intervene before disease progresses."

The STAMPEDE trials have already transformed care for patients with advanced prostate cancer, showing that adding treatments like abiraterone and docetaxel to hormone therapy improves survival. STAMPEDE2 is now testing additional treatment approaches, and this Prostate Cancer Foundation-funded research will help scientists build on STAMPEDE2 analyses by exploring not just whether ¹⁷⁷Lu-PSMA-617 works earlier in metastatic hormone-sensitive prostate cancer, but why it works in some patients and how resistance develops. Dr. James and his team will then use this knowledge to identify possible new treatment strategies to prevent resistance.

"We now know that combining treatments helps patients with metastatic hormone-sensitive prostate cancer live longer," said Dr. James. "Our current work will help us understand why advanced prostate cancers stop responding to treatment, which patients will benefit most from which therapies, and how to identify resistance when there is still time to intervene. This award gives us the resources and the team we need to make real progress."

The Prostate Cancer Foundation TACTICAL Awards provide $5-10 million over 3-5 years to support large-scale, collaborative, multi-institutional studies that tackle the most lethal forms of prostate cancer. Since 2022, the Prostate Cancer Foundation has invested $42 million in these projects, an innovative funding strategy that embodies the Foundation’s legacy of accelerating transformative team science. In 2012, the Prostate Cancer Foundation invested $20 million in two international Prostate Cancer Dream Teams whose work revolutionized advanced prostate cancer treatment by creating the first comprehensive multi-omic map of metastatic prostate cancer, which fast-forwarded precision medicine. For instance, mutations in genes like BRCA1 and BRCA2 were found to be common in metastatic prostate cancer, a discovery that led to the FDA approval of a new class of drugs called PARP inhibitors, which are now helping prostate cancer patients with these gene changes live longer.

"The TACTICAL program embodies our commitment to supporting bold, large-scale, multi-institutional research that would not be supported through traditional funding streams," said Gina Carithers, President and CEO of the Prostate Cancer Foundation. "These awards bring together the best scientific minds from multiple institutions to tackle the most urgent challenges in lethal prostate cancer today. Dr. James and his colleagues have the expertise, the infrastructure, and now the resources to accelerate breakthroughs that will save and extend men's lives. This is the power of philanthropic investment in transformational cancer research — the ability to move quickly, think big, and pursue discoveries that will fundamentally change how we treat prostate cancer."

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the world’s leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has raised more than $1 billion to fund cutting-edge research through more than 2,615 research projects at 312 leading cancer centers, with a global footprint spanning 29 countries. Since PCF’s inception, and through its efforts, patients around the world are living longer, suffering fewer complications, and enjoying better quality of life. PCF is committed to the mission of ending death and suffering from this disease. Learn more at pcf.org.

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