2025
Co-targeting of epigenetic regulators and BCL-XL improves efficacy of immune checkpoint blockade therapy in multiple solid tumors
Senent Y, Fresquet V, Jiménez V, Valencia K, Exposito F, Martín-Úriz P, Camps G, Fernández-Pierola E, de Córdoba B, González-Huarriz M, Tamayo I, Remírez A, Moreno H, Serrano D, Ajona D, Alonso M, Lecanda F, Pineda-Lucena A, Prósper F, Sanmamed M, Calvo A, Martinez-Climent J, Pio R. Co-targeting of epigenetic regulators and BCL-XL improves efficacy of immune checkpoint blockade therapy in multiple solid tumors. Molecular Cancer 2025, 24: 154. PMID: 40442785, PMCID: PMC12123720, DOI: 10.1186/s12943-025-02352-4.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeBcl-xL inhibitorsBcl-xLSolid tumorsTumor cell linesHematologic malignanciesSolid tumor cell linesEfficacy of immune checkpoint blockade therapyEpigenetic regulationImmune checkpoint blockade therapyAnti-apoptotic protein Bcl-xLHuman colon cancer modelsPreclinical models of solid tumorsBCL-XL dependencyImmunosuppressive Treg cellsCheckpoint blockade therapyAnti-tumor responsesImmunogenic cell deathProlonged overall survivalProtein Bcl-xLColon cancer modelM1/M2 macrophage ratioMultiple solid tumorsModels of solid tumorsCell lines
2023
Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies
Li Q, Robinson M, Leveille E, Zhang C, Sun R, Cheng Z, Kume K, Cosgun K, Kothari S, Khanduja D, Nakada D, Müschen M. Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies. Blood 2023, 142: 418. DOI: 10.1182/blood-2023-190269.Peer-Reviewed Original ResearchSmall molecule inhibitorsDrug discovery toolNAMPT inhibitorsCompound screenCell type-specific targetsCell linesMolecule inhibitorsPurine/pyrimidine metabolismTumor cell linesEnergy metabolismSalvage biosynthesis pathwaySolid tumor cell linesB cell developmentCellular energy metabolismB cell signalingAmino acid metabolismCell cycle arrestDiscovery toolDepletion of metabolitesBiosynthesis pathwayCompetitive fitnessRate-limiting enzymeNAMPT deletionConditional mouse modelEnergy stress
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