PARP1 elevation

These findings indicated that a ''YB-1/PARP1'' loop conferred resistance to CDK4/6 inhibitors. Furthermore, interrupting the loop can enhance tumor killing in the xenograft tumor model, which provides a promising strategy against drug resistance in breast cancer.

By contrast, those features were reduced in mutated p53 cells. These results could implicate that patients with elevated PARP-1 expression and wild type p53 could benefit from PARP-1 inhibition therapies, meanwhile it could have adverse effects for those carrying mutated p53 tumours.

Safety evaluations demonstrated acceptable safety profile and no off-target toxicity in monkeys. These non-clinical data suggest the stability of linker in circulation but efficiently release the payload in tumors, and eventually, expanded the therapeutic window.Taken together, preclinical data suggest that YL201 could be a promising treatment strategy for B7-H3 positive cancer patients.

Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.

Sixty-three percent had breast cancer (N=10) and 87% received Olaparib (N=13)... In this small series of BRCAgm patients, RT with concurrent and/or adjuvant PARPi for BM was feasible and safe. Several patients had long intervals of intracranial PFS suggestive of heightened sensitivity to RT particularly with adjuvant PARPi. Future prospective studies in larger cohorts are warranted to determine the optimal timing of PARPi relative to brain RT.

In this small series of BRCA patients, RT with concurrent and/or adjuvant PARPi for BM was feasible and safe. Several patients had long intervals of intracranial PFS suggestive of heightened sensitivity to RT particularly with adjuvant PARPi. Future prospective studies in larger cohorts are warranted to determine the optimal timing of PARPi relative to brain RT.

The goals of the current work were to investigate the mechanism by which DAXX regulates proliferation at the level of PARP-1 and/or JNK and test if DAXX expression predicts sensitivity to carboplatin, paclitaxel, doxorubicin, the PARP-1 inhibitor olaparib, or the JNK inhibitor SP600125 in TNBC cells. These results suggest that DAXX is a critical growth regulator and predictor of response to carboplatin and paclitaxel in triple negative breast cancer cells. DAXX is necessary to activate the JNK pathway in response to carboplatin and it is this carboplatin-mediated JNK signaling that inhibits cell proliferation. Furthermore, DAXX limits PARP-1 activity and is necessary for increased sensitivity to carboplatin or paclitaxel.

OCCC cells expressing cytoplasmic EBP50 were significantly less susceptible to cisplatin (CDDP)-induced apoptosis compared to cells expressing membranous EBP50...Together, our data suggest that cytoplasmic EBP50 inhibits apoptosis and promotes OCCC survival through stabilization of PARP1 activity and modulation of the XIAP/BCL2/BAX axis. This may increase the likelihood of tumor recurrence, and we therefore suggest a combined analysis for EBP50 and PARP1 may have great utility in OCCC prediction and prognosis.