Related Experiment Video

Updated: Jun 3, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

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

Published on: November 19, 2019

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NXP800 Activates the Unfolded Protein Response, Altering AR and E2F Function to Impact Castration-Resistant Prostate

Jonathan Welti1, Denisa Bogdan1, Ines Figueiredo1

  • 1The Institute of Cancer Research, London, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 9, 2025
PubMed
Abstract

Insights

This study shows that targeting the heat shock factor 1 (HSF1) pathway with NXP800 inhibits growth in advanced prostate cancer models. This approach offers a new strategy for treatment-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Advanced prostate cancer remains a fatal disease with androgen receptor (AR) signaling as a key therapeutic target.
  • Resistance to current AR inhibitors is inevitable, necessitating novel treatment strategies.
  • Heat shock proteins (HSPs) play a critical role in AR activity and represent a potential therapeutic target.

Purpose of the Study:

  • To investigate the association between the Gene Ontology cellular response to heat gene expression signature and clinical outcomes in castration-resistant prostate cancer (CRPC).
  • To evaluate the efficacy of targeting the heat shock factor 1 (HSF1) pathway with NXP800 in preclinical models of treatment-resistant prostate cancer.

Main Methods:

  • Transcriptome analysis of CRPC cohorts to correlate heat response signature with survival.
  • In vitro and in vivo studies using NXP800 to target the HSF1 pathway in prostate cancer models.
  • Assessment of NXP800's impact on HSP72 expression, unfolded protein response, and AR/E2F activity.

Main Results:

  • The cellular response to heat gene expression signature is linked to AR signaling and poorer outcomes in CRPC.
  • Inhibition of the HSF1 pathway with NXP800 reduces HSP72 levels and activates the unfolded protein response.
  • NXP800 effectively inhibits AR- and E2F-mediated activity, leading to suppressed tumor growth in resistant prostate cancer models.

Conclusions:

  • NXP800 demonstrates significant antitumor activity in treatment-resistant prostate cancer models.
  • This HSF1-targeting strategy is effective against prostate cancer subtypes with limited therapeutic options.
  • NXP800 warrants further clinical development for advanced and treatment-resistant prostate cancer.

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