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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ATM and ATR inhibition increases radiosensitivity and cGAS-STING activation in prostate cancer

Nina van Campen1, Vera E Mekers1, Maaike W Looman1

  • 1Radiotherapy and OncoImmunology laboratory, department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.

Cytokine
|June 18, 2025
PubMed

Insights

Inhibiting ATM and ATR kinases increases prostate cancer cell sensitivity to radiation, enhancing cell death and activating immune pathways. This combination therapy shows promise for treating metastatic castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Cancer Biology
  • Radiotherapy Research

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) remains incurable despite available therapies.
  • Approximately 23% of mCRPC patients harbor DNA damage response (DDR) gene alterations.
  • DDR gene mutations can sensitize cancer cells to radiation and immunotherapy.

Purpose of the Study:

  • To investigate the impact of inhibiting ATM and ATR kinases on prostate cancer cell radiosensitivity.
  • To assess the effect of ATM and ATR inhibition on the cGAS-STING pathway activation post-irradiation.
  • To explore combination strategies for mCRPC treatment.

Main Methods:

  • Utilized three prostate cancer cell lines (PC3, DU145).
  • Administered ATM and ATR inhibitors, alone and in combination, with irradiation.
  • Measured cell death, radiosensitivity, cGAMP levels, and type I interferon gene expression.

Main Results:

  • ATM and ATR inhibition increased radiosensitivity in PC3 and DU145 cell lines.
  • Combined ATM and ATR inhibition significantly enhanced radiation-induced cell death.
  • ATM inhibition (alone or combined with ATR inhibition) boosted radiation-induced cGAMP levels and type I interferon signaling.

Conclusions:

  • ATM and ATR inhibition enhances prostate cancer cell radiosensitivity and promotes cell death.
  • Combined ATM and ATR inhibition with radiotherapy activates the cGAS-STING pathway and type I interferon response.
  • This approach holds promise for improving radiotherapy and immunotherapy combinations in mCRPC treatment.
Keywords:
ATMATRInterferonProstate cancerRadiotherapycGAS

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