Therapeutic approach for triple-negative breast Cancer through poly (ADP-ribose) Polymerase-1 inhibitors: Current update

Bioorg Chem. 2025 Aug:163:108558. doi: 10.1016/j.bioorg.2025.108558. Epub 2025 May 19.

Abstract

Breast cancer is a dangerous disease that is common worldwide. It comprises 25 % of all women's cancers and 12 % of all new cancer cases diagnosed. Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer that lacks the expression for three targetable biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2). TNBC accounts for 15-20 % of all breast cancers worldwide and is most prevalent in young African-American women, as well as premenopausal women. Unlike other types of breast cancer, TNBC has limited treatment options. Mutations in the Breast Cancer type 1 and type 2 genes (BRCA1/2) are associated with TNBC. However, researchers are investigating new approaches to treating this subtype. One promising area of research is focused on Poly (ADP-Ribose) Polymerases (PARPs), a family of enzymes involved in DNA repair. Inhibition of PARP-1 can led to the loss of DNA repair via BRCA-dependent mechanisms. PARP-1 inhibitors such as Olaparib, Rucaparib, Niraparib, and Talazoparib have shown promise in treating various types of cancer. These inhibitors are being tested both as monotherapy and in combination with other therapies, such as cytotoxic therapy or radiotherapy. This review article focuses on exploring the significance of PARP-1 inhibitors for TNBC. It delves into the mechanism of action and discusses current and future perspectives for using these inhibitors to treat TNBC.

Keywords: HER2; In silico; PARP-1 inhibitors; Poly (ADP-ribose) polymerases (PARPs); Triple-negative breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Female
  • Humans
  • Molecular Structure
  • Poly (ADP-Ribose) Polymerase-1* / antagonists & inhibitors
  • Poly (ADP-Ribose) Polymerase-1* / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors* / chemistry
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Antineoplastic Agents
  • Poly (ADP-Ribose) Polymerase-1
  • PARP1 protein, human