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Updated: Oct 4, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

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A novel small-molecule activator of unfolded protein response suppresses castration-resistant prostate cancer growth

Huang Chen1, Ying Miao1, Aiwu Bian1

  • 1East China Normal University, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Cancer Letters
|February 5, 2022
PubMed

Insights

A novel unfolded protein response (UPR) activator, WJ-644A, effectively inhibited prostate cancer cell proliferation and induced tumor regression in animal models, offering a new therapeutic strategy for castration-resistant prostate cancer (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Androgen receptor-targeted therapy is standard for castration-resistant prostate cancer (CRPC), but acquired resistance necessitates new treatments.
  • The unfolded protein response (UPR) can be a survival mechanism, but acute activation induces cancer cell death.
  • Metastatic CRPC remains incurable, highlighting the urgent need for alternative therapeutic strategies.

Purpose of the Study:

  • To investigate the therapeutic potential of novel small molecule WJ-644A as an unfolded protein response (UPR) activator for castration-resistant prostate cancer (CRPC).
  • To elucidate the mechanisms by which WJ-644A exerts its anti-cancer effects in CRPC models.

Main Methods:

  • In vitro and in vivo studies using prostate cancer cell lines and animal models.
  • Administration of WJ-644A to assess its impact on tumor growth and survival.
  • Analysis of cellular mechanisms including UPR activation, methuosis, and autophagy.

Main Results:

  • WJ-644A demonstrated potent inhibition of prostate cancer cell proliferation.
  • WJ-644A treatment led to significant tumor regression in animal models with a favorable safety profile.
  • Mechanistic studies revealed that WJ-644A activates UPR, inducing methuosis and autophagy in cancer cells.

Conclusions:

  • The unfolded protein response (UPR) is a viable therapeutic target for CRPC.
  • WJ-644A is a promising novel UPR activator with significant therapeutic potential for treating CRPC.
  • This study provides a foundation for developing WJ-644A as a new treatment option for advanced prostate cancer.
Keywords:
AutophagyEndoplasmic reticulum stressHigh-throughput screenMethuosis

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