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Novel Theranostic Agents for Neuroendocrine Prostate Cancer

Jason Lewis, PhD

Principal Investigators: Jason Lewis, PhD (Memorial Sloan Kettering Cancer Center), Michael Morris, MD (Memorial Sloan Kettering Cancer Center), Lisa Bodei, MD, PhD (Memorial Sloan Kettering Cancer Center), Himisha Beltran, MD (Dana-Farber Cancer Institute), Felix Feng, MD (University of California San Francisco), Samir Zaidi, MD, PhD (Memorial Sloan Kettering Cancer Center), John Poirier, PhD (NYU Grossman School of Medicine)

Co-Investigators: Kishore Pillarsetty, PhD (Memorial Sloan Kettering Cancer Center), Yu Chen, MD, PhD (Memorial Sloan Kettering Cancer Center), Anuradha Gopalan, MD (Memorial Sloan Kettering Cancer Center)

Young Investigators: Ryan Reddy, MD (Memorial Sloan Kettering Cancer Center), Salomon Tendler, MD, PhD (Memorial Sloan Kettering Cancer Center), Audrey Mauguen, PhD (Memorial Sloan Kettering Cancer Center)

Description:

  • Approximately 17% of patients with advanced prostate cancer eventually develop neuroendocrine prostate cancer (NEPC), which is typified by aggressiveness and extreme lethality.
  • Multiple challenges must be overcome to address the needs of NEPC patients, the most critical of which include developing a non-invasive diagnostic method for NEPC and developing novel treatment strategies that provide durable responses.
  • Jason Lewis and team will create novel diagnostic and therapeutic agents using newly developed antibodies that target the NEPC-specific protein, DLL3.
  • The team is conducting an ongoing clinical trial evaluating a DLL3-targeted imaging agent to identify patients with NEPC and collect biopsy samples of NEPC tumors. The team will use data and samples from this trial to validate DLL3 as a promising therapeutic and diagnostic (“theranostic”) target for patients with NEPC.
  • Novel DLL3-targeted theranostics developed in this project will be tested in preclinical NEPC models, and if promising, translated into clinical trials in patients.
  • The team will also develop a preclinical platform to identify and optimize DLL3 treatment combination strategies for future clinical trials.
  • If successful, this project will validate DLL3 as a theranostic target for the identification and treatment of patients with NEPC, and develop a novel clinic-ready DLL3-targeted PET-based agent and DLL3-targeted radioligand therapy.

What this means to patients:   This team will validate DLL3 as a theranostic target for the identification and treatment of patients with NEPC, a highly aggressive and currently untreatable form of advanced prostate cancer.  A novel DLL3-targeted PET-based diagnostic and DLL3-targeted radioligand therapy will be developed and readied for testing in clinical trials.  These studies will also aid in the identification of rational combinatorial strategies that synergize with DLL3-targeted agents. These results will lay the groundwork for the clinical trials of not only the theranostic proposed in this grant, but also for immunotherapeutics, antibody–drug conjugates, and other DLL3-directed strategies that are currently under development for both NEPC and small cell lung cancer (SCLC).

View all the PCF TACTICAL Award-Class of 2022 recipients.

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