2021
WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway
Guo E, Xiao R, Wu Y, Lu F, Liu C, Yang B, Li X, Fu Y, Wang Z, Li Y, Huang Y, Li F, Wu X, You L, Qin T, Lu Y, Huang X, Ma D, Mills G, Sun C, Chen G. WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. Journal Of Experimental Medicine 2021, 219: e20210789. PMID: 34825915, PMCID: PMC8628262, DOI: 10.1084/jem.20210789.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCD8-Positive T-LymphocytesCell Cycle ProteinsCell Line, TumorEndogenous RetrovirusesEnzyme InhibitorsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHumansImmune Checkpoint InhibitorsMice, Inbred BALB CMice, Inbred C57BLMice, Inbred NODMice, SCIDNeoplasms, ExperimentalProtein-Tyrosine KinasesPyrazolesPyrimidinonesRNA, Double-StrandedSignal TransductionTumor BurdenConceptsImmune checkpoint blockadeAnti-tumor immunityEndogenous retroviral elementsWEE1 inhibitionCheckpoint blockadeCD8+ T cell-dependent mannerSensitivity to immune checkpoint blockadeResponse to immune checkpoint blockadeAnti-tumor T cellsCombination of WEE1 inhibitorT cell-dependent mannerPathway-targeted therapiesMultiple tumor modelsPopulation of patientsEmergence of resistanceDown-regulating FoxM1Viral defense pathwaysPD-L1Tumor regressionCombination therapyTargeted therapyCombination partnerT cellsPatient selectionWEE1 inhibitor
2020
mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers.
Li F, Guo E, Huang J, Lu F, Yang B, Xiao R, Liu C, Wu X, Fu Y, Wang Z, Peng S, Lei Y, Guo Z, Li L, Xi L, Sun C, Liu S, Chen G. mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers. American Journal Of Cancer Research 2020, 10: 908-924. PMID: 32266099, PMCID: PMC7136919.Peer-Reviewed Original ResearchEpithelial ovarian cancerOvarian cancerReplication stressWEE1 inhibitorSynergistically inhibited tumor growthOvarian cancer cell linesCombination of Wee1Patient-derived xenograftsDNA replication stressHeterogeneity of patient tumorsOvarian cancer cellsActivated mTOR pathwaySubstrate dNTPCheckpoint deficiencyTP53 mutationsCancer cell linesPatient tumorsClinical efficacyFork stallingTumor growthCell cycleTherapeutic windowDrug combinationsWEE1 inhibitionG2/M checkpoint