Abstract
Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer. This review covers the current results of clinical trials testing and future directions for the field of PARP inhibitor development.
Highlights
The results showed significantly prolonged progression-free survival (PFS) with olaparib versus standard therapy (7.0 vs. 4.2 months; hazard ratio (HR), 0.58; 95% CI, 0.43–0.8; p < 0.001); Response rates were observed to be 59.9% vs. 28.8% [64]
For the phase III clinical trial, 634 patients were selected based on histological clinical stage II–III Triple-negative breast cancer (TNBC) with no previous therapy for potentially curative surgery—they were randomly assigned to two groups; group I was treated with 50 mg veliparib orally twice a day, with 12 weekly doses of 80 mg/m2 intravenous paclitaxel, and carboplatin administered every 3 weeks, for 4 cycles [81,82,83]
The conventional treatment presently prescribed in hospitals for TNBC depends primarily on the clinical stage of the disease and tolerability to treatment—usually accompanied by corticosteroids and drugs to control symptoms to reduce adverse effects such as inhibition of DNA and RNA synthesis, inhibition of the topoisomerase II enzyme, generation of free oxygen radicals, induction of histone eviction from chromatin, etc
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. ADPRE consists of the PARP1 homology protein, nisms repair genetic mutations other than those in BRCA genes, such as CDK12, which is produced by the catalytic activity of ADP-ribosyl transferase reactions [19]. Poly(ADP) ribosylation (PARylation) of PARP1 multiple proteins that have roles in different aspects of DNA damage repair. PARP trapping occurs via the NHEJ pathway at the replication fork via enzymes such as DNA-PK, XRCC4, and Ku70/80, which are employed to undertake the DNA repair process [31,32,33] Another pathway of MMEJ or NHEJ leads to chromosomal and genomic instability and causes tumor cell death or somatic mutations, as shown in Figure 3 [31]. Inhibitor of poly-adenosine diphosphate(ADP)ribose polymerase (PARP) 1/2 being developed for the treatment of BRCA1/2-mutant solid tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
