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2023 PCF Challenge Award

Modulation of Anti-Androgen Response by NSD2 in Castration-Resistant Prostate Cancer

Principal Investigators: Michael Shen, PhD (Columbia University Medical Center), Andrea Califano, PhD (Columbia University Medical Center), Johann de Bono, MD, PhD (The Institute of Cancer Research), Charles L. Sawyers, MD (Memorial Sloan Kettering Cancer Center)

Young Investigators: Jia Li, PhD (Columbia University Medical Center), Zhen Sun, PhD (Memorial Sloan Kettering Cancer Center), Alessandro Vasciaveo, PhD (Columbia University Medical Center)

Collaborators: Cory Abate-Shen, PhD (Columbia University Medical Center), Kristian Helin, PhD (The Institute of Cancer Research Cancer), Massimo Loda, MD (Weill Cornell Medicine), Chao Lu, PhD (Columbia University Medical Center)

Description:

  • Neuroendocrine prostate cancer (NEPC) is a highly aggressive and lethal form of metastatic castration-resistant prostate cancer (mCRPC), for which new treatments are urgently needed.
  • Dr. Michael Shen and colleagues have identified NSD2 as a key driver of NEPC, and have found that inhibiting NSD2 restores sensitivity of CRPC models to anti-androgen therapy. They propose that NSD2 is a highly promising therapeutic target in CRPC and NEPC.
  • In this project, the team will comprehensively define the mechanisms by which NSD2 drives NEPC development and progression, and test various drug development approaches to determine an optimal strategy for therapeutic inhibition of NSD2.
  • If successful this project will provide rationale and a path forward for the development of NSD2-inhibitors, which could be a new, effective treatment for patients with NEPC.

What this means to patients: Dr. Shen and team have identified NSD2 as a critical driver and promising therapeutic target in NEPC, one of the most aggressive forms of prostate cancer. This team will establish the fundamental conceptual basis for rational targeting of NSD2 in NEPC, elucidate the mechanisms of NSD2 action, and provide a foundation for early-phase clinical trials of NSD2 inhibitors.