Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy
Ueno D, Vasquez JC, Sule A, Liang J, van Doorn J, Sundaram R, Friedman S, Caliliw R, Ohtake S, Bao X, Li J, Ye H, Boyd K, Huang RR, Dodson J, Boutros P, Bindra RS, Shuch B. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy. Oncotarget 2022, 13: 1054-1067. PMID: 36128328, PMCID: PMC9477221, DOI: 10.18632/oncotarget.28273.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCarcinoma, Renal CellCitric Acid CycleDioxygenasesDNAFumarate HydrataseFumaratesHumansJumonji Domain-Containing Histone DemethylasesKidney NeoplasmsLysineMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSuccinate DehydrogenaseSuccinatesTemozolomideConceptsRenal cell carcinomaPoly ADP-ribose polymerase inhibitorsADP-ribose polymerase inhibitorsCell carcinomaSDH-deficient renal cell carcinomaPolymerase inhibitorsLow-dose temozolomideAggressive renal cell carcinomaHereditary cancer syndromesNovel therapeutic strategiesDeficient murine modelStandard dosingTMZ resultsMurine modelTherapeutic strategiesCombination treatmentCancer syndromesTumor growthHomologous recombination DNA repair pathwayAccumulation of fumarateHR deficiencyPARP inhibitionTemozolomideChemotherapyCarcinomaTOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor.
Jo U, Murai Y, Agama KK, Sun Y, Saha LK, Yang X, Arakawa Y, Gayle S, Jones K, Paralkar V, Sundaram RK, Van Doorn J, Vasquez JC, Bindra RS, Choi WS, Pommier Y. TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Molecular Cancer Therapeutics 2022, 21: 1090-1102. PMID: 35439320, PMCID: PMC9256811, DOI: 10.1158/1535-7163.mct-21-1000.Peer-Reviewed Original ResearchConceptsATR inhibitorsTop1 inhibitorsHomologous recombination deficiencyNovel molecular interactionApoptotic cell deathCancer cellsTop1 cleavage complexesAtaxia telangiectasiaCleavage complexesCell deathDNA damageHigher DNA damageMolecular interactionsDNA baseKinase inhibitorsI inhibitorMolecular pharmacologyMouse xenograftsTOP1Recombination deficiencyTopoisomerase I inhibitorInhibitorsTumor growthRad3Predictive biomarkers