2024
Targeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Berning P, Fonseca-Arce D, Leveille E, Kothari S, Davids M, Jellusova J, Müschen M. Targeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies. Blood 2024, 144: 1412. DOI: 10.1182/blood-2024-208598.Peer-Reviewed Original ResearchProtein degradationRepression of MYCTranscriptional repression of MYCTranscriptional repressionPromote survivalProteasome inhibitorsProtein degradation pathwaysCell typesN-terminal residuesInduce cell deathRefractory B-cell malignanciesB-cateninB-cell malignanciesRNAi screenInteractome studiesB cell selectionRepressive complexesGene dependenciesProteasomal degradationB cellsChemogenomic screensProteasome inhibitor bortezomibActivated mycDeletion of Ctnnb1Cell death
2023
Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathway