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Interplay between ADP-Ribosylation and Androgen Receptor Function in Prostate Cancer.

Gali Sri Venkata Sai Rishma Reddy1, Krishna Samanta2, Pulak Kar1

  • 1Department of Biological Sciences, SRM University-AP, Amaravati, 522240, India.

Current Pharmaceutical Design
|April 20, 2026
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Summary
This summary is machine-generated.

Poly (ADP-ribose) polymerase (PARP) enzymes regulate androgen receptor (AR) signaling in prostate cancer. Understanding AR-PARP interactions may improve PARP inhibitor and AR inhibitor combinations for advanced prostate cancer therapy.

Keywords:
ADP-ribosylationAndrogen receptor (AR)MARylation and PARylationPARP enzymesPARP inhibitorsprostate cancer

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Androgen receptor (AR) signaling is crucial for prostate physiology and cancer progression.
  • Poly (ADP-ribose) polymerase (PARP) mediated ADP-ribosylation is a key regulator of AR activity.
  • PARP inhibitors (PARPi) are effective for BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).

Purpose of the Study:

  • To review the interplay between ADP-ribosylation and AR signaling in prostate cancer.
  • To emphasize the roles of distinct PARP enzymes in AR activity and therapeutic response.
  • To discuss the potential of this regulatory network for future advanced prostate cancer therapies.

Main Methods:

  • Review of current knowledge on AR signaling and ADP-ribosylation.
  • Focus on the roles of PARP7, PARP9/DTX3L, and PARP enzymes.
  • Analysis of MARylation and PARylation in prostate tumorigenesis.

Main Results:

  • PARP7 and PARP9/DTX3L directly modulate AR function and gene expression.
  • PARP enzymes regulate AR via MARylation and PARylation, impacting AR-PARP crosstalk.
  • Clinical trials show promise in combining PARPi with AR signaling inhibitors, but efficacy in non-HRR mutated tumors is unclear.

Conclusions:

  • The complex interplay between ADP-ribosylation and AR signaling is central to prostate cancer.
  • Targeting AR-PARP crosstalk offers potential for novel therapeutic strategies.
  • Further research may lead to improved combination therapies benefiting more prostate cancer patients.