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2025 Igor Tulchinsky – PCF Challenge Award

Harnessing Extracellular Vesicle and Cell-Free RNA Transcriptomics to Identify Novel Targets in Lethal Stem Cell-Like mCRPC

Principal Investigators: Oliver Sartor, MD (Tulane University), Jacob Orme, MD, PhD (Mayo Clinic), Aadel Chaudhuri, MD, PhD (Mayo Clinic), Elisa Ledet, PhD (Tulane University), Fabrice Lucien-Matteoni, PhD (Tulane University), Russell Pachynski, MD (Washington University), Christopher Maher, PhD (Washington University)

Co-Investigator: Jingqin Luo, PhD (Washington University)

Young Investigator: Pradeep Chauhan, PhD (Mayo Clinic)   

Description:

  • Prostate cancer that has spread throughout the body and no longer responds to hormone therapy—called metastatic castration-resistant prostate cancer (mCRPC)—remains a fatal disease. Despite important advances over the past two decades, most patients with this aggressive form of prostate cancer still die within two years of diagnosis. While doctors now have several treatments that can extend patients’ lives, these treatments eventually stop working.
  • Scientists have made tremendous progress in understanding the genetic mutations that drive prostate cancer. However, knowing about these mutations hasn’t always translated into effective treatments for several reasons including: Many mutations can’t be targeted with drugs, the cancer is too diverse with different cells having different genetic profiles, and we still don’t know all the genetic factors that make prostate cancer lethal.
  • In this project, Dr. Sartor and team aim to identify proteins on the surface of cancer cells that can be used as effective therapeutic targets, with a focus on the most aggressive, lethal forms of prostate cancer.
  • The team will use patient blood samples to identify new treatment targets. By analyzing genetic material and tiny vesicles (membrane enriched fragments) released from tumor cells that circulate in the bloodstream, the team will identify distinct subtypes of lethal prostate cancer and potentially find vulnerabilities on cancer stem-like cells—the most dangerous cells that can regenerate tumors and resist treatment.
  • If successful, this project will identify druggable prostate cancer cell surface proteins that are associated with cancer lethality and stemness, and will guide the development of new therapies for patients.

What this means to patients: The ability to characterize patients with the most lethal form of prostate cancer and match them to treatments targeting defined cell surface targets will transform advanced prostate cancer into a more manageable disease. Dr. Sartor and team will perform comprehensive molecular profiling of accessible prostate cancer surface proteins using patient blood samples, to uncover actionable vulnerabilities and guide more effective therapeutic strategies for lethal prostate cancer.