BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Fiskus W, Mill CP, Perera D, Birdwell C, Deng Q, Yang H, Lara BH, Jain N, Burger J, Ferrajoli A, Davis JA, Saenz DT, Jin W, Coarfa C, Crews CM, Green MR, Khoury JD, Bhalla KN. BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma. Leukemia 2021, 35: 2621-2634. PMID: 33654205, PMCID: PMC8410602, DOI: 10.1038/s41375-021-01181-w.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBiomarkers, TumorBridged Bicyclo Compounds, HeterocyclicCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansLymphoma, Large B-Cell, DiffuseMicePiperidinesProteinsProteolysisSulfonamidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLarge B-cell lymphomaB-cell lymphomaRichter transformationBET protein inhibitorLymphoma burdenImproved survivalCombination therapyC-Myc levelsEffective therapyNovel therapiesCell lymphomaXenograft modelProtein inhibitorTherapyBET inhibitorsProtein expressionCLLGenetic alterationsLymphomaInhibitorsIRF4Single-cell RNA-seqHuman modelCRISPR knockoutCellsMutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600