Related Experiment Video

Updated: Jun 13, 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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Notch as a Driver of Lineage Plasticity and Therapeutic Target in Enzalutamide-Resistant Prostate Cancer

Yuyin Jiang, Siyuan Cheng, Longjun Li

    Biorxiv : the Preprint Server for Biology
    |June 12, 2025
    PubMed

    Insights

    Notch signaling drives resistance to prostate cancer therapies like enzalutamide by promoting lineage plasticity. Inhibiting Notch signaling can overcome this resistance, offering a new therapeutic strategy for advanced prostate cancer.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cell Signaling

    Background:

    • Therapeutic resistance to androgen receptor (AR)-targeted therapies is a major obstacle in treating castration-resistant prostate cancer (CRPC).
    • Lineage plasticity is a key mechanism underlying treatment failure, but its molecular drivers are not fully understood.
    • The Notch signaling pathway is implicated in cell fate determination and cancer progression.

    Purpose of the Study:

    • To investigate the role of the Notch signaling pathway in mediating lineage plasticity and therapeutic resistance in CRPC.
    • To determine if Notch signaling activity is altered during prostate cancer progression and resistance.
    • To evaluate the potential of targeting Notch signaling to overcome enzalutamide resistance.

    Main Methods:

    • Transcriptomic analysis to assess Notch pathway activity.
    • Functional assays, including CRISPR-mediated gene knockout and pharmacological inhibition of Notch signaling.
    • In vitro studies to evaluate the impact of Notch inhibition on enzalutamide resistance.

    Main Results:

    • Notch signaling activity was found to be elevated during prostate cancer progression and in resistant tumors.
    • CRISPR-mediated knockout of Notch components reversed enzalutamide resistance in vitro.
    • Targeted inhibition of Notch signaling also demonstrated efficacy in overcoming enzalutamide resistance in vitro.

    Conclusions:

    • Notch signaling dynamically alters during prostate cancer progression and is a critical driver of therapeutic resistance.
    • Targeting the Notch pathway represents a promising therapeutic strategy to combat resistance to AR-targeted therapies in advanced prostate cancer.
    • Notch signaling is a druggable target for overcoming treatment resistance in castration-resistant prostate cancer.

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