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Purpose:. PARP inhibitors are approved for the treatment of high-grade serous ovarian cancers (HGSOC). Therapeutic resistance, resulting from restoration of homologous recombination (HR) repair or replication fork stabilization, is a pressing clinical problem. We assessed the activity of prexasertib, a checkpoint kinase 1 (CHK1) inhibitor known to cause replication catastrophe, as monotherapy and in combination with the PARP inhibitor olaparib in preclinical models of HGSOC, including those with acquired PARP inhibitor resistance. Experimental Design:. Prexasertib was tested as a single agent or in combination with olaparib in 14 clinically annotated and molecularly characterized luciferized HGSOC patient-derived xenograft (PDX) models and in.
Activation of ferroptosis, a recently described mechanism of regulated cell death, dramatically inhibits growth of ovarian cancer cells. Given the importance of lipid metabolism in ferroptosis and the key role of lipids in ovarian cancer, we examined the contribution to ferroptosis of stearoyl-CoA desaturase (SCD1, SCD), an enzyme that catalyzes the rate-limiting step in monounsaturated fatty acid synthesis in ovarian cancer cells. SCD1 was highly expressed in ovarian cancer tissue, cell lines, and a genetic model of ovarian cancer stem cells. Inhibition of SCD1 induced lipid oxidation and cell death. Conversely, overexpression of SCD or exogenous administration of its C16:1 and C18:1 products, palmitoleic acid or oleate, protected cells fr.
Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case–control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable.
Pharmafile 10/11/2019 04:43
NICE has announced it has made an about-face on its earlier ruling for Clovis Oncology’s Rubraca (rucaparib), revealing that the drug will now be made available immediately via the Cancer Drugs Fund (CDF) for women in England with relapsed ovarian, fallopian tube or peritoneal cancer, that has responded to platinum-based chemotherapy. The UK watchdog originally turned down the therapy due to concerns over the certainty of the data submitted, as well as over cost-effectiveness, based on the price put forward by Clovis.
Healio News 10/10/2019 07:35
Phase 1, open-label study evaluating the safety and efficacy of adoptive transfer of autologous NY-ESO-1 CD8-TCR engineered T cells and NY-ESO-1 CD4-TCR engineered hematopoietic stem cells after a myeloablative conditioning regimen, with administration of IL-2 in patients with relapsed or treatment-refractory ovarian, fallopian tube or primary peritoneal cancer.

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