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Clinical Application of PARP1 Inhibitors and Challenges in Cancer Therapy

Yunlin Luo1, Mingcheng Nie1, Yuekang Chen1

  • 1Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China.

Current Cancer Drug Targets
|January 8, 2025
PubMed

Insights

Poly(ADP-ribose) Polymerase 1 (PARP1) inhibitors show promise in cancer therapy by targeting DNA repair. This review details their mechanisms, clinical uses, and challenges in treating various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Poly(ADP-ribose) Polymerase 1 (PARP1) is crucial for DNA damage repair and a validated cancer therapy target.
  • PARP inhibitors (PARPi) disrupt DNA repair by trapping PARP1 on damaged DNA, leading to cancer cell death.

Purpose of the Study:

  • To review the role of PARP1 in DNA repair pathways.
  • To elucidate the mechanisms of PARP inhibitors (PARPi).
  • To summarize the clinical applications of authorized PARPi in various cancers.

Main Methods:

  • Literature review of PARP1 function in DNA repair.
  • Analysis of PARPi mechanisms, including PARylation inhibition and trapping PARP1.
  • Systematic summary of clinical data for six authorized PARPi (olaparib, rucaparib, niraparib, talazoparib, fuzuloparib, pamiparib).

Main Results:

  • PARP1 inhibition and trapping induce Transcription-replication Conflicts (TRCs), a key anti-cancer mechanism.
  • Six PARPi are authorized for monotherapy and combination treatments across diverse cancers.
  • Challenges and resistance mechanisms associated with PARPi therapy were identified.

Conclusions:

  • PARP1 inhibitors represent a significant advancement in cancer treatment.
  • Despite challenges and resistance, ongoing development of novel PARP1 inhibitors holds promise.
  • Further research into PARP1 inhibitors is essential for optimizing cancer therapy.
Keywords:
PARP inhibitorsPARP1PARylationcancer therapydrug resistance.olaparib

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