The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin
نویسندگان
چکیده
Supplementary Figure S1: (A) IC50 of proliferation after treatment with Olaparib: 72 hours versus 6 days. (B) Grafic representation of IC50 of ES cell lines after treatment with Olaparib with regard to ES cell lines1q status. (C) Grafic representation of IC50 of ES cell lines with regard to their p53 status.
منابع مشابه
Correction: The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin
Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh...
متن کاملPARP Inhibitors Sensitize Ewing Sarcoma Cells to Temozolomide-Induced Apoptosis via the Mitochondrial Pathway.
Ewing sarcoma has recently been reported to be sensitive to poly(ADP)-ribose polymerase (PARP) inhibitors. Searching for synergistic drug combinations, we tested several PARP inhibitors (talazoparib, niraparib, olaparib, veliparib) together with chemotherapeutics. Here, we report that PARP inhibitors synergize with temozolomide (TMZ) or SN-38 to induce apoptosis and also somewhat enhance the cy...
متن کاملCombining PARP-1 inhibition and radiation in Ewing sarcoma results in lethal DNA damage.
Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1). The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the expression of PARP-1, which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. I...
متن کاملSynergistic Effect of Trabectedin and Olaparib Combination Regimen in Breast Cancer Cell Lines
PURPOSE Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast ca...
متن کاملXI-006 induces potent p53-independent apoptosis in Ewing sarcoma
There is an imperious need for the development of novel therapeutics for the treatment of Ewing sarcoma, the second most prevalent solid bone tumour observed in children and young adolescents. Recently, a 4-nitrobenzofuroxan derivative, XI-006 (NSC207895) was shown to diminish MDM4 promoter activity in breast cancer cell lines. As amplification of MDM4 is frequently observed in sarcomas, this s...
متن کامل