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2022 Dr. Elliot and Nan Abramowitz – PCF Young Investigator Award

Investigating SSTR1 as a Novel Therapeutic Target for Acquired Resistance to Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer

Xiaolin Zhu, MD, PhD
University of California, San Francisco (UCSF)

Mentors: Felix Feng, MD, Rahul Aggarwal, MD, David Quigley, PhD

Description:

  • Androgen receptor (AR)-targeted therapies, including abiraterone and enzalutamide, are widely used to treat advanced prostate cancer and have significantly improved patient outcomes. Unfortunately, resistance to these treatments inevitably develops, and the duration of response is particularly short in most patients with metastatic castration-resistant prostate cancer (mCRPC).
  • Understanding and overcoming resistance to AR-targeted therapies is an important area of prostate cancer research.
  • Dr. Xiaolin Zhu is studying the molecular mechanisms of resistance to AR-targeted therapies in mCRPC, and previously identified downregulation of SSTR1 as a possible mechanism.
  • In this project, Dr. Zhu and colleagues will investigate the role of SSTR1 in resistance to AR-targeted therapies in preclinical models of mCRPC.
  • Whether agents that activate SSTR1 can reduce tumor drug resistance to AR-targeted therapies will be investigated in preclinical models.
  • In addition, the mechanisms by which SSTR1 is downregulated in mCRPC will be studied using samples from patients with mCRPC.
  • If successful, this project will determine the role of SSTR1 in resistance to AR-targeted therapies and establish its potential as a new therapeutic target.

What this means to patients: The development of resistance to AR-targeted therapies is a critical problem in the treatment of mCRPC. Dr. Zhu’s project will determine whether and how downregulation of SSTR1 plays a role in this process, and whether targeting SSTR1 can prevent development or progression of mCRPC. This may provide rationale for clinical trials investigating SSTR1 agonists as a potential novel therapy for patients with mCRPC.