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2024 The John & Daria Barry Foundation – PCF Young Investigator Award

A Theranostic Approach: Targeted Alpha Therapy of Delta-Like Ligand 3 Expressing Neuroendocrine Prostate Cancer

Salomon Tendler, MD, PhD
Memorial Sloan Kettering Cancer Center

Mentors: Jason Lewis, PhD; Michael Morris, MD

Description:

  • Neuroendocrine derived prostate cancer (NEPC) is an exceptionally lethal tumor type, present in ~20-25% of patients with metastatic castration resistant prostate cancer (mCRPC). NEPC has an almost universal loss of key cell cycle regulators leading to exceptional tumor cell sensitivity to radiation. However, NEPC is typically a diffusely metastatic disease, not amenable to external beam radiation approaches. 
  • Dr. Salomon Tendler is developing a novel radioligand therapy for NEPC that targets the NEPC-associated protein DLL3. Radioligand therapies are systemically delivered treatments composed of tumor targeted molecules attached to potent radioactive isotopes. 
  • The team will test various DLL3-targeted antibodies and chemistry approaches to develop an optimal DLL3-targeted radioligand therapy that carries the alpha particle emitting isotope Actinium-225.
  • Preclinical biodistribution, dosimetry, and safety studies will be performed to identify a candidate with optimal therapeutic properties and a proposed dosing strategy in preparation for clinical trials.
  • If successful, this project will develop a novel first-in-class treatment option for NEPC, that is ready for testing in clinical trials.

What this means to patients: NEPC is an aggressive and incurable form of prostate cancer, present in ~1/4 of patients with highly advanced disease. Dr. Tendler’s project will develop a novel DLL3-targeted radioligand therapy optimal for testing in clinical trials in patients with NEPC. This project has the potential to significantly improve outcomes and prolong survival without severely impacting NEPC patients’ quality of life.