vlx600 has been researched along with Ovarian-Neoplasms* in 2 studies
2 other study(ies) available for vlx600 and Ovarian-Neoplasms
| Article | Year |
|---|---|
VLX600 Disrupts Homologous Recombination and Synergizes with PARP Inhibitors and Cisplatin by Inhibiting Histone Lysine Demethylases.
Tumors with defective homologous recombination (HR) DNA repair are more sensitive to chemotherapies that induce lesions repaired by HR as well as PARP inhibitors (PARPis). However, these therapies have limited activity in HR-proficient cells. Accordingly, agents that disrupt HR may be a means to augment the activities of these therapies in HR-proficient tumors. Here we show that VLX600, a small molecule that has been in a phase I clinical trial, disrupts HR and synergizes with PARPis and platinum compounds in ovarian cancer cells. We further found that VLX600 and other iron chelators disrupt HR, in part, by inhibiting iron-dependent histone lysine demethylases (KDM) family members, thus blocking recruitment of HR repair proteins, including RAD51, to double-strand DNA breaks. Collectively, these findings suggest that pharmacologically targeting KDM family members with VLX600 may be a potential novel strategy to therapeutically induce HR defects in ovarian cancers and correspondingly sensitize them to platinum agents and PARPis, two standard-of-care therapies for ovarian cancer. Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Cisplatin; Clinical Trials, Phase I as Topic; DNA Breaks, Double-Stranded; DNA Repair; Drug Resistance, Neoplasm; Drug Synergism; Female; Histone Demethylases; Homologous Recombination; Humans; Hydrazones; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Triazoles; Tumor Cells, Cultured | 2021 |
BRCA1 Deficiency Upregulates NNMT, Which Reprograms Metabolism and Sensitizes Ovarian Cancer Cells to Mitochondrial Metabolic Targeting Agents.
BRCA1 plays a key role in homologous recombination (HR) DNA repair. Accordingly, changes that downregulate BRCA1, including Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; BRCA1 Protein; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cyclin-Dependent Kinases; DNA Methylation; Energy Metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Hydrazones; Hydroxybenzoates; Mice; Mitochondria; Mutation; Nicotinamide N-Methyltransferase; Ovarian Neoplasms; Ovary; Oxidative Phosphorylation; Promoter Regions, Genetic; Tigecycline; Triazoles; Up-Regulation; Xenograft Model Antitumor Assays | 2019 |