Related Experiment Video

Updated: Sep 19, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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BCL2 drives castration resistance in castration-sensitive prostate cancer by orchestrating reciprocal crosstalk

Rahim Hirani1, Subhiksha Nandakumar2, Nabila Zaman3

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Cell Reports
|May 31, 2025
PubMed

Insights

Androgen-deprivation therapy (ADT) resistance in prostate cancer is linked to BCL2 upregulation. Inhibiting BCL2 with ADT may delay castration-resistant prostate cancer (CRPC) progression in early stages.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate cancer progression after androgen-deprivation therapy (ADT) leads to castration resistance and is a major cause of cancer-related death.
  • There is a lack of identified driver alterations associated with ADT resistance in castration-sensitive prostate cancer (CSPC).

Purpose of the Study:

  • To investigate the role of cell signaling crosstalk in early ADT resistance in CSPC.
  • To explore the potential of targeting BCL2 in combination with ADT for prostate cancer treatment.

Main Methods:

  • Analysis of RNA sequencing data from clinical trials.
  • Preclinical experiments to study signaling pathways.

Main Results:

  • Nearly universal upregulation of BCL2 was observed in CSPC cells following ADT.
  • BCL2 was found to mediate reciprocal signaling between androgen receptor (AR)-BCL2 and phosphatidylinositol 3-kinase (PI3K) pathways.
  • This crosstalk appears to drive the transformation of CSPC to castration-resistant prostate cancer (CRPC) after ADT.

Conclusions:

  • BCL2 plays a critical role in the transition from CSPC to CRPC.
  • BCL2 inhibition combined with ADT may be a viable strategy to impede or delay CRPC development in CSPC patients.
  • BCL2 inhibition may be less effective in patients who have already developed CRPC.
Keywords:
ADTARBCL 2CP: CancerHedgehogPI3 kinase signalingcellular plasticitycombination therapyprostate cancersignalingvenetoclax

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