2025
Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma.
Greenman M, Demirkiran C, Bellone S, Hartwich T, McNamara B, Ettorre V, Santin N, Sethi N, Yang-Hartwich Y, Papatla K, Ratner E, Santin A. Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma. Cancer Research Communications 2025, 5: 774-782. PMID: 40299780, PMCID: PMC12062949, DOI: 10.1158/2767-9764.crc-25-0057.Peer-Reviewed Original ResearchConceptsTrophoblast cell surface antigen 2Uterine serous carcinomaAntibody-dependent cell-mediated cytotoxicityAntibody-drug conjugatesCell-mediated cytotoxicitySerous carcinomaPreclinical activityCell linesTargets trophoblast cell-surface antigen-2Presence of peripheral blood lymphocytesTreatment of uterine serous carcinomaInduce antibody-dependent cell-mediated cytotoxicityPrimary USC cell linesRecurrent uterine serous carcinomaUSC xenograftsUterine serous carcinoma cell linesAntigen 2In vivoPrimary tumor cell linesTROP2 overexpressionBiomarker-targeted therapiesControl ADCChromium release assayHigher recurrence rateTumor growth suppressionFAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
Lubrano S, Cervantes-Villagrana R, Faraji F, Ramirez S, Sato K, Adame-Garcia S, Officer A, Arang N, Rigiracciolo D, Anguiano Quiroz P, Martini C, Wang Y, Ferguson F, Bacchiocchi A, Halaban R, Coma S, Holmen S, Pachter J, Aplin A, Gutkind J. FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma. Cancer Cell 2025, 43: 428-445.e6. PMID: 40020669, PMCID: PMC11903146, DOI: 10.1016/j.ccell.2025.02.001.Peer-Reviewed Original ResearchConceptsBRAF V600E melanomaFocal adhesion kinaseV600E melanomaFAK inhibitorActivated focal adhesion kinaseFocal adhesion kinase inhibitionRaf-MEKActivation of focal adhesion signalingFocal adhesion kinase inhibitorResistance to BRAFiSyngeneic mouse modelMAPK pathway inhibitionFocal adhesion signalingPro-apoptotic activityMelanoma patientsAdhesion signalingImmune therapyBRAF mutationsBRAFiTranscriptome analysisMelanomaMouse modelPathway inhibitionBRAFMelanoma cellsAn antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy
Schrank B, Wang Y, Wu A, Tran N, Lee D, Edwards J, Huntoon K, Dong S, Ha J, Ma Y, Grippin A, Jeong S, Antony A, Chang M, Kang M, Gallup T, Koong A, Li J, Yun K, Kim B, Jiang W. An antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy. Nature Cancer 2025, 6: 511-527. PMID: 40000910, DOI: 10.1038/s43018-025-00919-0.Peer-Reviewed Original ResearchConceptsAntibody-toxin conjugatesTumor cellsImmune recognition of tumor cellsEnhanced antigen cross-presentationRecognition of tumor cellsCancer cell phagocytosisTumor-derived antigensToxin listeriolysin OTumor-derived peptidesImproved animal survivalPromote immune recognitionCytosolic immune sensorsIntracellular bacterium Listeria monocytogenesTreatment in vivoTreating multiple cancersPhagocytosis checkpointsCheckpoint blockadeCancer immunotherapySignal CD47Listeriolysin OMetastatic breastMelanoma tumorsTherapeutic strategiesAnimal survivalCell phagocytosisDevelopment of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisitionLipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation
Liu J, Shen Y, Liu J, Xu D, Chang C, Wang J, Zhou J, Haffty B, Zhang L, Bargonetti J, De S, Hu W, Feng Z. Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation. Nature Communications 2025, 16: 1762. PMID: 39971971, PMCID: PMC11839913, DOI: 10.1038/s41467-025-57099-9.Peer-Reviewed Original ResearchConceptsGain-of-functionTumor suppressive function of p53Mutp53 accumulationAccumulate to high levelsFunction of p53Mutant p53 accumulationTumor suppressive functionMutant p53Subcutaneous xenograft tumor modelMutp53Promote tumorigenesisP53 accumulationPalmitoylationPotential therapeutic strategyXenograft tumor modelFASNTumor modelTumor organoidsTransgenic miceTherapeutic strategiesP53Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis
Nair R, Vu A, Freer A, Bhatia K, Wang D, Savani M, Matulis S, Lonial S, Jaye D, Boise L, Seo S, Corson T, Nooka A, Bhatt S, McBrayer S, Gupta V, Hu X, Barwick B, Reddi A, Shanmugam M. Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis. Blood 2025, 145: 732-747. PMID: 39693611, DOI: 10.1182/blood.2024025690.Peer-Reviewed Original ResearchConceptsElectron transport chainBcl-2Heme biosynthesisBCL-2 antagonismElectron transport chain activityIron-containing prosthetic groupMultiple myelomaB-cell lymphoma 2MEK-ERK signalingGene signatureActivation of prosurvivalApoptotic thresholdPurine biosynthesisPenultimate enzymePyrimidine biosynthesisMetabolic rewiringTransport chainProtein kinaseMultiple Myeloma Research Foundation CoMMpass studyBiosynthesisPurine synthesisGenetic profilePrimary MM cellsProsthetic groupProgression-free survivalα-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+
Blackburn J, Islam Q, Benlaouer O, Tonevitskaya S, Petitto E, Ushkaryov Y. α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2+. Toxins 2025, 17: 73. PMID: 39998090, PMCID: PMC11860464, DOI: 10.3390/toxins17020073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalcium SignalingCell Line, TumorHumansMaleMiceMice, Inbred C57BLNeuromuscular JunctionSpider VenomsConceptsAbsence of extracellular Ca<sup>2+</sup> anRelease of stored Ca2+Store-operated Ca<sup>2+</sup> entryExtracellular Ca<sup>2+</sup>Absence of extracellular Ca2Nerve terminalsCytosolic Ca<sup>2+</sup>Neurotransmitter releaseOpening of Ca<sup>2+</sup> channelsControl of neurotransmitter releaseRelease of neurotransmittersIntracellular storesExtracellular Ca2BAPTA-AMG protein-coupled receptorsMouse neuromuscular junctionCation ionophoreSensitive to inhibitorsCa2+Neuromuscular junctionNerveNeurotransmitterPhysiological controlReleaseInfluxtRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells
Miao S, Li H, Song X, Liu Y, Wang G, Kan C, Ye Y, Liu R, Li H. tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells. Journal Of Experimental Medicine 2025, 222: e20240559. PMID: 39873720, PMCID: PMC11774205, DOI: 10.1084/jem.20240559.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsTumor-killing functionTransfer RNARegulating cholesterol biosynthesisAntitumor immunityCapacity of CD8+ T cellsActivation of CD8+ T cellsCholesterol biosynthesisM1A modificationTumor-killing capacityAntitumor responseATP citrate lyaseCancer immunotherapyCD8Effector functionsMetabolic reprogrammingProtein translationBiosynthetic demandsCitrate lyaseIn vitro assaysIn vivoPosttranscriptional mechanismsRegulatory checkpointsBiosynthesisSLC25A38 is required for mitochondrial pyridoxal 5’-phosphate (PLP) accumulation
Pena I, Shi J, Chang S, Yang J, Block S, Adelmann C, Keys H, Ge P, Bathla S, Witham I, Sienski G, Nairn A, Sabatini D, Lewis C, Kory N, Vander Heiden M, Heiman M. SLC25A38 is required for mitochondrial pyridoxal 5’-phosphate (PLP) accumulation. Nature Communications 2025, 16: 978. PMID: 39856062, PMCID: PMC11760969, DOI: 10.1038/s41467-025-56130-3.Peer-Reviewed Original ResearchConceptsPyridoxal 5'-phosphateGenome-wide CRISPR interference screenPyridoxal 5'-phosphate-dependent enzymeCRISPR interference screenSerine hydroxymethyltransferase-2Active form of vitamin B6One-carbon unitsImpaired cellular proliferationAmino acid metabolismOne-carbon metabolismInterference screenEssential proteinsMolecular machineryNucleotide synthesisCongenital sideroblastic anemiaProliferation defectSLC25A38Acid metabolismErythroleukemia cellsOrnithine aminotransferaseActive formK562 cellsEnzymatic reactionsCellular proliferationPolyamine synthesisExploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma
Yang L, Pham K, Xi Y, Wu Q, Liu D, Robertson K, Liu C. Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma. PLOS ONE 2025, 20: e0317401. PMID: 39841705, PMCID: PMC11753693, DOI: 10.1371/journal.pone.0317401.Peer-Reviewed Original ResearchConceptsGlypican-3Hepatocellular carcinomaCAR-NKNatural killerCell linesCAR-NK therapyCAR-NK cellsTreatment of hepatocellular carcinomaNK cell lineAnti-tumor effectsCancer-related mortalitySuppressed tumor growthPrimary liver cancerInfluence therapeutic outcomesCells in vitroHepatocellular carcinoma treatmentHepG2 cells in vitroNK92MI cellsImmunotherapy strategiesNSG miceImmunotherapy targetOncofetal glycoproteinTherapy resistanceImprove patient outcomesPoor prognosisGPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis
Ristić D, Bärnthaler T, Gruden E, Kienzl M, Danner L, Herceg K, Sarsembayeva A, Kargl J, Schicho R. GPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis. Frontiers In Immunology 2025, 15: 1513547. PMID: 39885986, PMCID: PMC11779727, DOI: 10.3389/fimmu.2024.1513547.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaModel of pancreatic ductal adenocarcinomaImmune tumor microenvironmentTumor microenvironmentT cellsKO miceEndocannabinoid systemWT miceTumor growthCD8<sup>+</sup> T cellsG protein-coupled receptor 55Suppress T cell functionCancer cellsMurine pancreatic ductal adenocarcinomaCD3<sup>+</sup> T cellsExpression of PDL1T cell influxImmune cell compositionT cell functionTumor microenvironment cellsMigration of T cellsReduced tumor weightImmune cell populationsT cell activationCell linesQuantitative Glycan-Protein Cross-Linking Mass Spectrometry Using Enrichable Linkers Reveals Extensive Glycan-Mediated Protein Interaction Networks
Chen S, Xie Y, Alvarez M, Sheng Y, Bouchibti Y, Chang V, Lebrilla C. Quantitative Glycan-Protein Cross-Linking Mass Spectrometry Using Enrichable Linkers Reveals Extensive Glycan-Mediated Protein Interaction Networks. Analytical Chemistry 2025, 97: 1584-1593. PMID: 39805041, PMCID: PMC11780575, DOI: 10.1021/acs.analchem.4c04134.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCross-Linking ReagentsGlycopeptidesGlycoproteinsHumansMass SpectrometryPolysaccharidesProtein Interaction MapsConceptsProtein-protein interactionsProtein interaction networkCell surface glycansTerminal sialic acidAbundant membrane proteinProtein pairsCross-linking mass spectrometrySurface glycansAffinity purificationInteraction networkSialylated glycoformsMembrane proteinsLysine residuesProtein networkTarget proteinsSialic acidGlycansBiotin groupPolypeptide moietyProteinInteractomeExtensive interactionsCell membranePeptide pairsPolypeptideBile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi S, Chen D, Liu Y, Johnson M, Miller C, Ganguly S, Lande K, LaPorta M, Hoffmann F, Mann T, Teneche M, Casillas E, Mangalhara K, Mathew V, Sun M, Jensen I, Farsakoglu Y, Chen T, Parisi B, Deota S, Havas A, Lee J, Chung H, Schietinger A, Panda S, Williams A, Farber D, Dhar D, Adams P, Feng G, Shadel G, Sundrud M, Kaech S. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 2025, 387: 192-201. PMID: 39787217, DOI: 10.1126/science.adl4100.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsBile Acids and SaltsCarcinoma, HepatocellularCD8-Positive T-LymphocytesCell Line, TumorEndoplasmic Reticulum StressHepatocytesHumansImmune Checkpoint InhibitorsImmunotherapyLithocholic AcidLiver NeoplasmsMiceOxidative StressProgrammed Cell Death 1 ReceptorTumor MicroenvironmentUrsodeoxycholic AcidConceptsTumor-specific T-cell responsesT cell responsesAnti-programmed cell death protein 1Ursodeoxycholic acidCell death protein 1CD8<sup>+</sup> T cellsBile acidsFeatures of human hepatocellular carcinomaImprove tumor immunotherapyInfluence antitumor immunityT cell functionReduced tumor growthBA synthesisLiver cancer modelCancer model systemsHuman hepatocellular carcinomaLandscape of cancerAntitumor immunityTumor immunotherapySecondary bile acidsOrgan-specific metabolitesEndoplasmic reticulum stressT cellsCancer modelsDietary intakeSorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A 1H/23Na Spectroscopic Imaging Study
Khan M, Walsh J, Kurdi S, Mishra S, Mihailović J, Coman D, Hyder F. Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A 1H/23Na Spectroscopic Imaging Study. NMR In Biomedicine 2025, 38: e5319. PMID: 39764672, DOI: 10.1002/nbm.5319.Peer-Reviewed Original ResearchConceptsU87 tumorsSorafenib-treated tumorsUpregulated aerobic glycolysisSodium-potassium pumpInterstitial spaceTumor microenvironmentIntracellular NaTumor growthSpectroscopic imaging studiesTumor invasionGlioblastoma modelSodium levelsTumorGlioblastoma therapyImaging studiesPlaceboSorafenibMetabolic changesImmune functionCancer hallmarksAerobic glycolysisProliferative stateMeasure treatment effectsIonic changesProliferation rate
2024
Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt J, Ferreira L, Jesus C, Woodward T, Oliva I, Xu Z, Crystal J, Pepin R, Silverman R, Hohmann A. Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2318833121. PMID: 39793055, PMCID: PMC11725897, DOI: 10.1073/pnas.2318833121.Peer-Reviewed Original ResearchConceptsComplete Freund's adjuvantInflammatory painMechanical hypersensitivityAntinociceptive efficacyGlutamate levelsInjection of complete Freund's adjuvantConditioned place preference assayPaclitaxel-induced mechanical hypersensitivitySpinal site of actionSide effectsEnhancement of GABAergic transmissionChemotherapeutic agent paclitaxelPaclitaxel-induced increaseCompared to morphineLumbar spinal cordIncreased endogenous GABA levelsReduced glutamate levelsNeuropathic nociceptionSite of actionGABAergic transmissionAnalgesic strategiesPathological painGABAergic inhibitionSpinal sitesAbuse liabilityTRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling
Lu W, Zalmas L, Bailey C, Black J, Martinez-Ruiz C, Pich O, Gimeno-Valiente F, Usaite I, Magness A, Thol K, Webber T, Jiang M, Saunders R, Liu Y, Biswas D, Ige E, Aerne B, Grönroos E, Venkatesan S, Stavrou G, Karasaki T, Al Bakir M, Renshaw M, Xu H, Schneider-Luftman D, Sharma N, Tovini L, Jamal-Hanjani M, McClelland S, Litchfield K, Birkbak N, Howell M, Tapon N, Fugger K, McGranahan N, Bartek J, Kanu N, Swanton C. TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling. Nature Cell Biology 2024, 27: 154-168. PMID: 39738653, PMCID: PMC11735399, DOI: 10.1038/s41556-024-01558-w.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCadherinsCarcinoma, Non-Small-Cell LungCell Line, TumorChromosomal InstabilityGene Expression Regulation, NeoplasticHippo Signaling PathwayHumansLung NeoplasmsMiceMitosisProtein Serine-Threonine KinasesSignal TransductionTranscription FactorsYAP-Signaling ProteinsConceptsWhole-genome doublingStructural chromosome instabilityChromosomal instabilityHomologous recombinationNumerical chromosome instabilityNon-small-cell lung cancerHR deficiencyPersistent replication stressGenome doublingRadial chromosomesHippo signalingReplication stressChromosomal translocationsEvolutionary adaptationDriver eventsGenetic alterationsFAT1Increased tumor heterogeneityChromosomeCO depletionYAP1Downstream mechanismsRepair deficiencyIntratumour heterogeneityExperimental approachChk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation
Black E, Ramírez Parrado C, Trier I, Li W, Joo Y, Pichurin J, Liu Y, Kabeche L. Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation. Nature Communications 2024, 15: 10782. PMID: 39737931, PMCID: PMC11685634, DOI: 10.1038/s41467-024-54922-7.Peer-Reviewed Original ResearchConceptsPolo-like kinase 1Plk1 activityChromosome segregationMitotic polo-like kinase 1Mitotic chromosome segregationProtecting genome stabilitySensitivity to PLK1 inhibitorsMitotic cell divisionCheckpoint kinase 2Polo-like kinase 1 activityDNA damage repairGenome stabilityChromosome missegregationCytokinetic defectsCell divisionGenomic instabilityT-loopCell cycleKinase activityChromosome misalignmentMitotic errorsChk2Kinase 2Damage repairChromosomeHigh p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis
Park S, Roh T, Tanaka Y, Kim Y, Park S, Kim T, Eom S, Park T, Park I, Kim S, Kim J. High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis. Neoplasia 2024, 60: 101116. PMID: 39724755, PMCID: PMC11729681, DOI: 10.1016/j.neo.2024.101116.Peer-Reviewed Original ResearchConceptsP16<sup>INK4a</sup> expressionImmune cell infiltrationTumor cellsCell infiltrationImmunologically active tumor microenvironmentInfiltration of T cellsActive tumor microenvironmentTERT promoter mutationsExtended overall survivalIsocitrate dehydrogenase (IDH)-wildtypeSecretion of chemokinesSenescent phenotypeMalignant brain tumorsIn vitro studiesEGFR amplificationOverall survivalTumor microenvironmentCDKN2A/2B deletionT cellsPrognostic markerImprove prognosisP16INK4a expressionPromoter mutationsTumorBrain tumorsTertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction
Gao X, Tang X, Tu Z, Yu J, Bao Y, Long G, Sheu W, Wu H, Liu J, Zhou J. Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction. Biomaterials 2024, 317: 123035. PMID: 39731842, PMCID: PMC11827167, DOI: 10.1016/j.biomaterials.2024.123035.Peer-Reviewed Original ResearchConceptsSurvival of tumor-bearing miceBrain tumorsEffective treatmentPenetrate brain tumorsEffective treatment of glioblastomaTumor-bearing micePrimary brain tumorTreatment of glioblastomaMitochondria-targeted effectsTreating glioblastomaCancer treatmentGlioblastomaEffective killingTherapeutic targetHexokinase inhibitorGBM cellsPyroptosis inductionMitochondriaTumorGlycyrrhetinic acidTargeting effectTreatmentComparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups
Olkowski C, Basuli F, Fernandes B, Ghaemi B, Shi J, Zhang H, Farber J, Escorcia F, Choyke P, Jacobson O. Comparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups. Molecular Pharmaceutics 2024, 22: 533-543. PMID: 39680709, DOI: 10.1021/acs.molpharmaceut.4c01101.Peer-Reviewed Original Research
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