2023
Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma
Ruiz C, Garcia C, Jacox J, Lawres L, Muzumdar M. Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma. Life Science Alliance 2023, 6: e202302228. PMID: 37648285, PMCID: PMC10474221, DOI: 10.26508/lsa.202302228.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinogenesisCell Transformation, NeoplasticHumansObesityPancreatic NeoplasmsConceptsPancreatic adenocarcinomaPreclinical modelsObesity-cancer connectionObesity-associated cancersMicrobial dysbiosisHormone dysregulationEarly progressionRisk factorsWorldwide prevalencePancreatic tumorigenesisObesityPreclinical modelingCancer typesCancer developmentTumor cellsAdenocarcinomaTumor initiationCancerMetabolic stateCellular metabolismNovel strategyDysbiosisInflammationTherapyPrevalence
2019
Identification of DHODH as a therapeutic target in small cell lung cancer
Li L, Ng SR, Colón CI, Drapkin BJ, Hsu PP, Li Z, Nabel CS, Lewis CA, Romero R, Mercer KL, Bhutkar A, Phat S, Myers DT, Muzumdar MD, Westcott PMK, Beytagh MC, Farago AF, Vander Heiden MG, Dyson NJ, Jacks T. Identification of DHODH as a therapeutic target in small cell lung cancer. Science Translational Medicine 2019, 11 PMID: 31694929, PMCID: PMC7401885, DOI: 10.1126/scitranslmed.aaw7852.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsBiphenyl CompoundsCarcinoma, Pancreatic DuctalCell Line, TumorDCMP DeaminaseDihydroorotate DehydrogenaseDisease ProgressionEnzyme InhibitorsHumansLung NeoplasmsMiceMolecular Targeted TherapyOxidoreductases Acting on CH-CH Group DonorsPancreatic NeoplasmsPyrimidinesSmall Cell Lung CarcinomaSurvival AnalysisXenograft Model Antitumor AssaysConceptsSmall cell lung cancerCell lung cancerPancreatic ductal adenocarcinomaLung cancerLung adenocarcinomaMouse modelSCLC cellsTherapeutic targetHuman patient-derived xenograft modelsAggressive lung cancer subtypePatient-derived xenograft modelsLung cancer subtypesAutochthonous mouse modelPotential therapeutic targetSCLC tumor growthGenetic driver eventsTreatment landscapePoor prognosisDuctal adenocarcinomaXenograft modelCancer subtypesTumor growthPharmacological inhibitionDihydroorotate dehydrogenaseGenetic vulnerability
2018
iRGD-guided tumor-penetrating nanocomplexes for therapeutic siRNA delivery to pancreatic cancer
Lo JH, Hao L, Muzumdar MD, Raghavan S, Kwon EJ, Pulver EM, Hsu F, Aguirre AJ, Wolpin BM, Fuchs CS, Hahn WC, Jacks T, Bhatia SN. iRGD-guided tumor-penetrating nanocomplexes for therapeutic siRNA delivery to pancreatic cancer. Molecular Cancer Therapeutics 2018, 17: molcanther.1090.2017. PMID: 30097486, PMCID: PMC6298224, DOI: 10.1158/1535-7163.mct-17-1090.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancerCancer-related deathReceptor expression patternsSite of diseasePDAC cell linesMol Cancer TherTherapeutic trialsAutochthonous tumorsDuctal adenocarcinomaMouse modelStromal barrierTumor growthSystemic deliveryNeuropilin-1Peptide iRGDTumor-penetrating abilityThree-dimensional organoidsSiRNATumor targetingCell linesTherapyCancerStromaIRGD
2016
Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers
Muzumdar MD, Dorans KJ, Chung KM, Robbins R, Tammela T, Gocheva V, Li CM, Jacks T. Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Nature Communications 2016, 7: 12685. PMID: 27585860, PMCID: PMC5025814, DOI: 10.1038/ncomms12685.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell ProliferationCyclin-Dependent Kinase Inhibitor p16Disease ProgressionGene Expression Regulation, NeoplasticLung NeoplasmsMiceMice, TransgenicPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Tumor Cells, CulturedTumor Suppressor Protein p53ConceptsLung adenomasLow-grade pancreatic intraepithelial neoplasiaP53 lossEarly tumor progressionPancreatic intraepithelial neoplasiaAdvanced adenocarcinomaIntraepithelial neoplasiaPancreatic tumorsP53 knockoutSolid tumorsOncogenic KrasTumor progressionSuppressive roleTumor developmentExtensive cellular heterogeneityLineage-related cellsP53AdenomasTumorsCancerContiguous growthDouble markersProgressionDistinct clonesDifferential expression