The mechanism and efficacy of PARP inhibitors have been well studied in some cancers, especially homologous recombination (HR)-deficient ovarian cancer and breast cancer, yet such studies are still relatively fewer in lung cancer.
Staining of p53 and PARP1 in breast cancer TMAs and comparison with the TCGA database indicated a higher double-positive signal in basal-like breast cancer than in Luminal A or Luminal B subtypes.
PARP inhibitors have recently been approved as monotherapies for the treatment of recurrent ovarian cancer and metastatic <i>BRCA</i>-associated breast cancer, and ongoing studies are exploring additional indications and combinations with other agents.
The use of PARP inhibitors in other cancers with homologous recombination repair deficiencies, such as breast cancer and prostate cancer, is gradually evolving as well, including their use in the neoadjuvant and adjuvant settings.
Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types.
Although PARP1 was found at BRG1 positive/H3K27ac negative promoters of highly expressed genes in a transformed breast cancer cell line, its transcriptional activity was limited to genes simultaneously controlled by BRG1 and EP300, indicating that the ADP-ribosylation of EP300 plays a dominant role in the regulation of BRG1-EP300-driven transcription.
Among Iranian women, the association between PARP1 polymorphisms and BC was never studied before so in this case-control study, the genetic association of three SNPs (rs1136410, rs907187 and rs4653734) was analyzed with susceptibility to BC.
A Comparative Study of the Anticancer Activity and PARP-1 Inhibiting Effect of Benzofuran-Pyrazole Scaffold and Its Nano-Sized Particles in Human Breast Cancer Cells.
To this end, by encapsulating the miR-451 mimic and PARP1 inhibitor in the same cationic liposome, we examined the potential of enhancing the response of PARP1 inhibition on BRCA1-deficient breast cancer by regulating the PI3K pathway.
Knockdown of GALNT6 in breast cancer cell attenuated the protein expression of PCNA, cyclin D1, C-myc and β-catenin, and increased the expression of E-cadherin, caspase 3 and cleaved PARP1.
In this scenario, the goal of this study was to identify novel prototypes of PARP-1 inhibitors for the development of antitumor therapeutics to treat breast cancer.
The data provide insight into the mechanism of action of PARP inhibitors in <i>BRCA</i>-associated breast cancer.<i>This article is highlighted in the In This Issue feature, p. 681</i>.
We hypothesized that PARP1 activity mediated tamoxifen resistance in ERα-positive breast cancer and that combining the antiestrogen tamoxifen with a PARP1 inhibitor (PARPi) would sensitize tamoxifen resistant cells to tamoxifen therapy.
PARP inhibitors represent one of the successful models of translational research in this area and clinical data showed high efficacy and reasonable toxicity with these agents in patients with breast cancer and BRCA mutation.
In vitro study revealed the antiproliferative and proapoptotic effects of essential oils of <i>T. vulgaris</i> in MCF-7 and MDA-MB-231 cells (analyses of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS); 5-bromo-20-deoxyuridine (BrdU); cell cycle; annexin V/PI; caspase-3/7; Bcl-2; PARP; and mitochondrial membrane potential).<i>T. vulgaris</i> L. demonstrated significant chemopreventive and therapeutic activities against experimental breast carcinoma.
The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP.
These data suggest that PARP-1 is vital for DSB repair in breast cancer cells when Alt-EJ is activated.-Huang, Y., Shao, Q., Luo, X., Yang, D., Zeng, B., Xiang, T., Ren, G., Cheng, Q. Poly(ADP-ribose) polymerase-1 promotes recruitment of meiotic recombination-11 to chromatin and DNA double-strand break repair in Ku70-deficient breast cancer cells.
It is known that the PARP inhibitor, olaparib, has a significant synthetic lethal effect on tumors with BRCA 1/2 mutations, particularly in ovarian and breast cancer.
Drugs targeting DDR pathways taking advantage of clinical synthetic lethality have already shown therapeutic benefit - for example, the PARP inhibitor olaparib has shown benefit in <i>BRCA</i>-mutant ovarian and breast cancer.
Inhibition of mTOR downregulates expression of DNA repair proteins and is highly efficient against BRCA2-mutated breast cancer in combination to PARP inhibition.