Featured Publications
Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma
Chung KM, Singh J, Lawres L, Dorans KJ, Garcia C, Burkhardt DB, Robbins R, Bhutkar A, Cardone R, Zhao X, Babic A, Vayrynen SA, Dias Costa A, Nowak JA, Chang DT, Dunne RF, Hezel AF, Koong AC, Wilhelm JJ, Bellin MD, Nylander V, Gloyn AL, McCarthy MI, Kibbey RG, Krishnaswamy S, Wolpin BM, Jacks T, Fuchs CS, Muzumdar MD. Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma. Cell 2020, 181: 832-847.e18. PMID: 32304665, PMCID: PMC7266008, DOI: 10.1016/j.cell.2020.03.062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell LineCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDisease ProgressionEndocrine CellsExocrine GlandsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLMutationObesityPancreatic NeoplasmsSignal TransductionTumor MicroenvironmentConceptsPancreatic ductal adenocarcinomaPDAC progressionDuctal adenocarcinomaMajor modifiable risk factorModifiable risk factorsBeta cell expressionObesity-associated changesAutochthonous mouse modelPancreatic ductal tumorigenesisDriver gene mutationsPeptide hormone cholecystokininRisk factorsPDAC developmentMouse modelObesityHormone cholecystokininOncogenic KrasCell expressionTumor microenvironmentDietary inductionCancer developmentGene mutationsReversible roleMurine samplesProgression
2024
Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer.
Sogunro A, Muzumdar M. Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer. Cancer Research 2024, 84: 2935-2937. PMID: 39279380, DOI: 10.1158/0008-5472.can-24-1474.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTumor microenvironmentAntitumor effectPancreatic cancerObese micePhysical activityAdvanced tumor growthSystemic cytokine productionMyeloid cell infiltrationPancreatic ductal adenocarcinoma developmentEffect of obesityHigh-fat diet-induced obesityDiet-induced obesitySyngeneic allograftsAdvanced tumorsProtumorigenic effectsLean miceWhite adipose tissueCell infiltrationDuctal adenocarcinomaObesity-associatedTumor growthCytokine productionImpact of physical activityInflammatory cytokinesPerioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer
Cecchini M, Salem R, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend J, Cai G, Chowdhury S, Yugawa D, Tseng R, Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan S, Cha C, Billingsley K, Kunstman J, Johung K, Wiess C, Muzumdar M, Spickard E, Aushev V, Laliotis G, Jurdi A, Liu M, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer. JAMA Oncology 2024, 10: 1027-1035. PMID: 38900452, PMCID: PMC11190830, DOI: 10.1001/jamaoncol.2024.1575.Peer-Reviewed Original ResearchProgression-free survivalPancreatic ductal adenocarcinomaOverall survivalCtDNA levelsPhase 2 nonrandomized controlled trialAnalysis of circulating tumor DNAMedian progression-free survivalResectable pancreatic ductal adenocarcinomaControlled trialsAssess surgical candidacyBaseline ctDNA levelModified 5-fluorouracilResectable pancreatic cancerPancreatic protocol computed tomographyAssociated with recurrenceTumor molecular featuresAggressive malignant tumorKaplan-Meier estimatesRandomized clinical trialsStandard of careCtDNA-positivePreoperative cyclesNonrandomized controlled trialsUnresectable diseaseModified FOLFIRINOX
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 linesTherapyCancerStromaIRGDDifferences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer
Tao Z, Muzumdar MD, Detappe A, Huang X, Xu ES, Yu Y, Mouhieddine TH, Song H, Jacks T, Ghoroghchian PP. Differences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer. Nano Letters 2018, 18: 2195-2208. PMID: 29533667, PMCID: PMC5957485, DOI: 10.1021/acs.nanolett.7b04043.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaHuman pancreatic ductal adenocarcinomaPancreatic tumorsMouse modelAutochthonous modelPoor overall prognosisAutochthonous mouse modelAutochthonous tumor modelTumor cell clustersOverall prognosisSurvival outcomesPancreatic cancerDuctal adenocarcinomaTransplanted tumorPreclinical studiesFree drug formulationDense stromaPreclinical testingTumor modelTumorsOxaliplatinNoninvasive optical imagingAnticancer agentsAnticancer drugsTherapeutic formulationsAdaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells
Chen PY, Muzumdar M, Dorans KJ, Robbins R, Bhutkar A, Del Rosario A, Mertins P, Qiao J, Schafer AC, Gertler F, Carr S, Jacks T. Adaptive and Reversible Resistance to Kras Inhibition in Pancreatic Cancer Cells. Cancer Research 2018, 78: 985-1002. PMID: 29279356, PMCID: PMC5837062, DOI: 10.1158/0008-5472.can-17-2129.Peer-Reviewed Original ResearchConceptsMurine PDAC cellsPDAC cellsNontranscriptional mechanismsKRAS inhibitorsGlobal phosphoproteomic profilingActivated KRASHallmark genetic alterationsTranscriptional changesPhosphoproteomic profilingCell signalingCell statesPathway componentsTumor-initiating capacityPancreatic ductal adenocarcinomaTemporal controlGenetic alterationsCell morphologyMechanistic directionsKras expressionKrasCellsProliferative kineticsInhibitorsNovel KRAS inhibitorsAdherence properties
2017
Survival of pancreatic cancer cells lacking KRAS function
Muzumdar MD, Chen PY, Dorans KJ, Chung KM, Bhutkar A, Hong E, Noll EM, Sprick MR, Trumpp A, Jacks T. Survival of pancreatic cancer cells lacking KRAS function. Nature Communications 2017, 8: 1090. PMID: 29061961, PMCID: PMC5653666, DOI: 10.1038/s41467-017-00942-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBenzimidazolesCarcinoma, Pancreatic DuctalDNA Copy Number VariationsHumansImmunoblottingIndazolesMiceMorpholinesPancreatic NeoplasmsPhenylurea CompoundsPiperidinesProto-Oncogene MasProto-Oncogene Proteins p21(ras)PurinesPyrimidinesPyrimidinonesQuinazolinonesSulfonamidesThiazolesConceptsMitogen-activated protein kinasePDAC cellsCRISPR/Cas-mediated genome editingDependent mitogen-activated protein kinaseKRAS inhibitionGene expression profilesMetastasis-related genesProto-oncogene KRASGenome editingProtein kinasePI3K inhibitorsExpression profilesDeficient cellsPancreatic cancer cellsMechanisms of responsePDAC resistanceKRAS functionInduced sensitivityPancreatic ductal adenocarcinomaRole of KRASK inhibitorsCancer cellsKRAS inhibitorsAbsolute dependenceSubset of humans