Research Progress of PARP Inhibitor Monotherapy and Combination Therapy for Endometrial Cancer

Curr Drug Targets. 2022;23(2):145-155. doi: 10.2174/1389450122666210617111304.

Abstract

Endometrial cancer is one of the three most common malignant tumors in the female reproductive system. Advanced and recurrent endometrial cancers have poor prognoses and lack effective treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors have been applied to many different types of tumors, and they can selectively kill tumor cells that are defective in homologous recombination repair. Endometrial cancer is characterized by mutations in homologous recombination repair genes; accordingly, PARP inhibitors have achieved positive results in off-label treatments of endometrial cancer cases. Clinical trials of PARP inhibitors as monotherapies and within combination therapies for endometrial cancer are ongoing. For this review, we searched PubMed with "endometrial cancer" and "PARP inhibitor" as keywords, and we used "olaparib", "rucaparib", "niraparib" and "talazoparib" as search terms in clinicaltrials.gov for ongoing trials. The literature search ended in October 2020, and only English-language publications were selected. Multiple studies confirm that PARP inhibitors play an important role in killing tumor cells with defects in homologous recombination repair. Its combination with immune checkpoint inhibitors, PI3K/AKT/mTOR pathway inhibitors, cell cycle checkpoint inhibitors, and other drugs can improve the treatment of endometrial cancer.

Keywords: PARP inhibitor; PI3K/AKT/mTOR pathway inhibitor.; combination therapy; endometrial cancer; homologous recombination deficiency; immune checkpoint inhibitor; targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / genetics
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Phosphatidylinositol 3-Kinases
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases / metabolism

Substances

  • Antineoplastic Agents
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases