2025
CRISPR-Cas13d Functional Transcriptomics Reveals Widespread Isoform-Selective Cancer Dependencies on LncRNAs
Morelli E, Aktas Samur A, Maisano D, Gao C, Favasuli V, Papaioannou D, De Nola G, Henninger J, Liu N, Turi M, Folino P, Vreux L, Cumerlato M, Chen L, Aifantis I, Fulciniti M, Anderson K, Lytton-Jean A, Gulla A, Young R, Samur M, Munshi N. CRISPR-Cas13d Functional Transcriptomics Reveals Widespread Isoform-Selective Cancer Dependencies on LncRNAs. Blood 2025 PMID: 40403231, DOI: 10.1182/blood.2025028746.Peer-Reviewed Original ResearchCRISPR-Cas13dMultiple myelomaTE-lncRNAsIsoform-specific functionsDiverse cancer cell linesMM patientsCancer cell linesCellular proteostasisSubcellular localizationTumor cellsClinical dataCancer transcriptomeCytosolic isoformEndoplasmic reticulumFunctional transcriptomeHeat shock proteinsCancer dependenciesMM-specificClinical relevanceAnimal modelsLong noncoding RNAsLncRNA transcriptomeTherapeutic potentialCharacterize hundredsTranscriptomeAzenosertib is a potent and selective WEE1 kinase inhibitor with broad antitumor activity across a range of solid tumors.
Ma J, Liu W, Li J, Kim D, Kim S, Levy A, Cai Z, Bunker K, Recio-Boiles A, Segar J, Sen S, Doroshow D, Jandial D, Rutgard M, Harismendy O, Grant S, Samatar A, Fischer K, Lackner M. Azenosertib is a potent and selective WEE1 kinase inhibitor with broad antitumor activity across a range of solid tumors. Molecular Cancer Therapeutics 2025, of1-of15. PMID: 40231599, DOI: 10.1158/1535-7163.mct-24-1194.Peer-Reviewed Original ResearchDNA damageMaintenance of genome integrityDNA damage response networkRegulate cell cycle progressionCell cycle checkpointsAccumulation of DNA damageCell cycle progressionInduction of apoptosisAnticancer therapeutic targetSolid tumorsGenome integrityCancer cell linesReplication stressCycle progressionGenomic instabilityAntitumor activityMitotic catastropheCell cyclePreclinical efficacy modelsAdvanced solid tumorsSolid tumor indicationsPhase I studyDamaged DNATumor growth inhibitionCessation of treatmentCyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers
Kim D, Chung H, Liu W, Jeong K, Ozmen T, Ozmen F, Rames M, Kim S, Guo X, Jameson N, de Jong P, Yea S, Harford L, Li J, Mathews C, Doroshow D, Charles V, Kim D, Fischer K, Samatar A, Jubb A, Bunker K, Blackwell K, Simpkins F, Meric-Bernstam F, Mills G, Harismendy O, Ma J, Lackner M. Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers. Npj Precision Oncology 2025, 9: 3. PMID: 39755818, PMCID: PMC11700143, DOI: 10.1038/s41698-024-00787-4.Peer-Reviewed Original ResearchUterine serous carcinomaSerous carcinomaCyclin E1 expressionOvarian cancer cell linesWEE1 kinase inhibitionE1 expressionPhase I studyClasses of chemotherapyUpregulation of cyclin E1Levels of replication stressIn vivo modelsCancer cell linesGynecologic malignanciesGynecologic cancerOncogenic driversCell cycle checkpointsClinical activityG1 to S phaseBaseline levelsMultiple cell cycle checkpointsActivity of CDK2Cell cycle progressionKinase inhibitionCell linesCyclin E1
2024
CGMega: explainable graph neural network framework with attention mechanisms for cancer gene module dissection
Li H, Han Z, Sun Y, Wang F, Hu P, Gao Y, Bai X, Peng S, Ren C, Xu X, Liu Z, Chen H, Yang Y, Bo X. CGMega: explainable graph neural network framework with attention mechanisms for cancer gene module dissection. Nature Communications 2024, 15: 5997. PMID: 39013885, PMCID: PMC11252405, DOI: 10.1038/s41467-024-50426-6.Peer-Reviewed Original ResearchTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerGrowth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex
Aladelokun O, Lu L, Zheng J, Yan H, Jain A, Gibson J, Khan S, Johnson C. Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex. Human Genomics 2024, 18: 67. PMID: 38886847, PMCID: PMC11184737, DOI: 10.1186/s40246-024-00635-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate-Ammonia LigaseCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell ProliferationColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHeterograftsHumansMaleMiceReceptors, EstrogenReceptors, G-Protein-CoupledSex FactorsXenograft Model Antitumor AssaysConceptsFemale tumor-bearing miceFemale CRC patientsTumor-bearing miceCRC patientsTumor growthInferior survivalAssociated with inferior survivalMetabolic reprogrammingG protein-coupled estrogen receptorTriggering metabolic reprogrammingSustained tumor growthSuppressed tumor growthExpression of asparagine synthetaseCancer cell linesBackgroundSex-related differencesSurvival improvementImpact of sexFemale miceEstrogen receptorCancer growthTranslational relevanceRewiring of metabolic pathwaysCancer burdenMetabolic pathwaysAsparagine synthetaseCEACAM5-Targeted Immuno-PET in Androgen Receptor–Negative Prostate Cancer
Imberti C, De Gregorio R, Korsen J, Hoang T, Khitrov S, Kalidindi T, Nandakumar S, Park J, Zaidi S, Pillarsetty N, Lewis J. CEACAM5-Targeted Immuno-PET in Androgen Receptor–Negative Prostate Cancer. Journal Of Nuclear Medicine 2024, 65: 1043-1050. PMID: 38782457, PMCID: PMC11218725, DOI: 10.2967/jnumed.123.267107.Peer-Reviewed Original ResearchConceptsNeuroendocrine prostate cancerCarcinoembryonic antigen-related cell adhesion molecule 5CEACAM5 expressionProstate cancerAggressive neuroendocrine prostate cancerAndrogen receptor (AR)-negativeEx vivo organ distributionXenograft prostate cancer modelsProstate cancer cell linesProstate cancer modelCell line LNCaP.Immuno-PET imagingCell line PC3Prostate cancer hallmarksCancer cell linesCancer modelsRadiolabeled antibodiesImmuno-PETSurface antigensProstatePET imagingCancerCancer hallmarksWestern blottingCell linesMutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Prosz A, Sahgal P, Huffman B, Sztupinszki Z, Morris C, Chen D, Börcsök J, Diossy M, Tisza V, Spisak S, Likasitwatanakul P, Rusz O, Csabai I, Cecchini M, Baca Y, Elliott A, Enzinger P, Singh H, Ubellaker J, Lazaro J, Cleary J, Szallasi Z, Sethi N. Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting. Npj Precision Oncology 2024, 8: 87. PMID: 38589664, PMCID: PMC11001913, DOI: 10.1038/s41698-024-00561-6.Peer-Reviewed Original ResearchNucleotide excision repairGastric cancer cell linesNucleotide excision repair-deficientPlatinum chemotherapyHR deficiencyCancer cell linesPARP inhibitorsHomologous recombinationGenome sequence dataSensitivity to platinum chemotherapySingle-cell RNA sequencingCell linesHR-deficient cancersDNA repair pathwaysSensitivity to cisplatinRad51 foci assaysMutational signature analysisSequence dataGenomic featuresWhole exomeInduce apoptosisRNA sequencingGastroesophageal adenocarcinomaRepair pathwaysHRD score
2023
FLED: a full-length eccDNA detector for long-reads sequencing data
Li F, Ming W, Lu W, Wang Y, Li X, Dong X, Bai Y. FLED: a full-length eccDNA detector for long-reads sequencing data. Briefings In Bioinformatics 2023, 24: bbad388. PMID: 37930031, PMCID: PMC10632013, DOI: 10.1093/bib/bbad388.Peer-Reviewed Original ResearchConceptsLong readsNanopore long-read sequencing technologyLong-read sequencing technologiesLong-read sequencing dataShort sequence readsCancer cell line samplesNanopore long readsCis-regulatory elementsExtrachromosomal circular DNAFull-length sequenceCell linesPolymerase chain reactionCancer-related genesCell line samplesRolling Circle AmplificationCancer-related pathwaysHigh-throughput detectionSequence readsEccDNA sequencingIntact geneEccDNACancer cell linesEccDNA moleculesLinear DNARegulatory potencySalvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions
Skinner O, Blanco-Fernández J, Goodman R, Kawakami A, Shen H, Kemény L, Joesch-Cohen L, Rees M, Roth J, Fisher D, Mootha V, Jourdain A. Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions. Nature Metabolism 2023, 5: 765-776. PMID: 37198474, PMCID: PMC10229423, DOI: 10.1038/s42255-023-00774-2.Peer-Reviewed Original ResearchConceptsUpper glycolysisGenome-wide genetic screenNutrient-limited conditionsNon-oxidative branchGenetic screenCancer lineagesContext of diseaseRegulated stepGrowth of cellsATP productionGlyceraldehyde 3Cancer cell linesGlucose transportPrimary macrophagesGlycolysisCell linesComplete lossPyrimidine synthesisPathwayRNACarbon building blocksAlternative nutrientsRibose moietyUridineComplete absenceAssessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens
Feng W, Inoue R, Kuwata T, Niikura N, Fujii S, Kumaki N, Honda K, Xu L, Goetz A, Gaule P, Cogswell J, Rimm D, McGee R. Assessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens. Applied Immunohistochemistry & Molecular Morphology 2023, 31: 339-345. PMID: 37093713, PMCID: PMC10155692, DOI: 10.1097/pai.0000000000001126.Peer-Reviewed Original ResearchConceptsNeutral buffered formalinNegative percentage agreementPositive percentage agreementOverall percentage agreementBreast cancerPercentage agreementHER2 statusHuman epidermal growth factor receptor 2 (HER2) statusEpidermal growth factor receptor 2 statusTumor samplesCell linesGastric cancer tumorsGastric cancer cell linesTumor tissue samplesClinical trial sitesCancer cell linesHER2 testingTumor specimensReal-world settingTumor tissueCancer tumorsBuffered formalinSitu hybridization assaysType of fixativeCentral laboratoryNRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8
Anandhan A, Dodson M, Shakya A, Chen J, Liu P, Wei Y, Tan H, Wang Q, Jiang Z, Yang K, Garcia J, Chambers S, Chapman E, Ooi A, Yang-Hartwich Y, Stockwell B, Zhang D. NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8. Science Advances 2023, 9: eade9585. PMID: 36724221, PMCID: PMC9891695, DOI: 10.1126/sciadv.ade9585.Peer-Reviewed Original ResearchConceptsLabile iron poolNFE2L2/Human ovarian cancer tissuesCancer cellsOvarian cancer cell linesOvarian cancer tissuesIntracellular labile iron poolIron homeostasisCancer cell linesPreclinical modelsNrf2 inhibitionCancer tissuesNrf2 levelsCancer treatmentFerroptotic deathNrf2Ferroptosis resistanceKnockout cellsCell linesUntapped strategyFerroptosisIron poolCellsHomeostasisExpressionThe Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo
Han C, McNamara B, Bellone S, Harold J, Manara P, Hartwich T, Mutlu L, Yang-Hartwich Y, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. Gynecologic Oncology 2023, 170: 172-178. PMID: 36706643, PMCID: PMC10023457, DOI: 10.1016/j.ygyno.2023.01.015.Peer-Reviewed Original ResearchConceptsCombination of olaparibOvarian cancerHER2 expressionSingle agentCell linesGynecologic cancer mortalityHER2-negative tumorsOvarian cancer cell linesOvarian cancer patientsEpithelial ovarian carcinomaNovel therapeutic optionsOC cell linesUnmet medical needPoly (ADP-ribose) polymerase (PARP) inhibitorsPan-ErbB inhibitorSingle-agent olaparibPolymerase inhibitor olaparibPoly (ADP-ribose) polymerase (PARP) inhibitor olaparibPrimary HER2Cancer cell linesNegative tumorsTherapeutic optionsCancer mortalityCancer patientsNeu expression
2022
The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines
Rezaeian A, Khatami F, Heidari Keshel S, Akbari M, Mirzaei A, Gholami K, Mohammadi Farsani R, Aghamir S. The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines. Scientific Reports 2022, 12: 20924. PMID: 36463254, PMCID: PMC9719468, DOI: 10.1038/s41598-022-23204-x.Peer-Reviewed Original ResearchConceptsExpression of epithelial to mesenchymal transitionCancer cell linesProstate cancerMesenchymal stem cells-derived exosomesCell linesCells-derived exosomesHormone-refractory prostate cancerMSC-exosomesKidney cancer cell linesPercentage of apoptotic cellsProliferation of cancer cellsDecreased Bcl2 expressionEpithelial to mesenchymal transitionAnti-angiogenic effectsRenal cancer cell linesGene expression changesRealtime PCR methodKidney tumor cell lineOsteopontin variantsTumor cell linesVEGF-CAntitumor effectBladder cancerHormone-sensitiveRenal cancerLactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells
Kshitiz, Afzal J, Suhail Y, Chang H, Hubbi M, Hamidzadeh A, Goyal R, Liu Y, Sun P, Nicoli S, Dang C, Levchenko A. Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells. Cell Systems 2022, 13: 1048-1064.e7. PMID: 36462504, PMCID: PMC10012408, DOI: 10.1016/j.cels.2022.11.003.Peer-Reviewed Original ResearchConceptsHIF-1α activityActivation of genesChaperone-mediated autophagyCancer cellsCell divisionIndividual cancer cellsRegulated processPatient-derived cancer cellsSubset of cellsMolecular mechanismsFluorescent reportersSingle-cell responsesCancer cell linesCell linesGenesHypoxic tumor cellsHIF-1αHypoxic conditionsCellsBroad suppressionAggressive growthTumor cellsHypoxic cellsOscillatory activityExtracellular lactateCombined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.
Ghosh S, Mazumdar T, Xu W, Powell RT, Stephan C, Shen L, Shah PA, Pickering CR, Myers JN, Wang J, Frederick MJ, Johnson FM. Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers. Clinical Cancer Research 2022, 28: 4479-4493. PMID: 35972731, PMCID: PMC9588713, DOI: 10.1158/1078-0432.ccr-22-1627.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAlphapapillomavirusApoptosisATPases Associated with Diverse Cellular ActivitiesAurora KinasesCell Cycle ProteinsFemaleHumansOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsRetinoblastoma ProteinUterine Cervical NeoplasmsConceptsHPV-positive cancer cellsInhibition-induced apoptosisAurora kinase inhibitorsAurora kinase inhibitionCancer cellsKinase inhibitionAbsence of RbViral oncoprotein E7Kinase inhibitorsMitotic exitAAA-ATPaseProtein degradationRb functionMechanisms of sensitivityPathway componentsTRIP13MAD2L1Extensive apoptosisCancer cell linesSquamous cancer cell linesApoptosisCell linesRetinoblastoma expressionBUB1BProtein expression correlatesFusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1)
Michikawa C, Gopalakrishnan V, Harrandah AM, Karpinets TV, Garg RR, Chu RA, Park YP, Chukkapallia SS, Yadlapalli N, Erikson-Carter KC, Gleber-Netto FO, Sayour E, Progulske-Fox A, Chan , Wu X, Zhang J, Jobin C, Wargo JA, Pickering CR, Myers JN, Silver N. Fusobacterium is enriched in oral cancer and promotes induction of programmed death-ligand 1 (PD-L1). Neoplasia 2022, 31: 100813. PMID: 35834946, PMCID: PMC9287628, DOI: 10.1016/j.neo.2022.100813.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAdjacent normal tissuesWhole-exome sequencingNormal tissuesNeck cancerOral tongue squamous cell carcinoma patientsTongue squamous cell carcinoma patientsSquamous cell carcinoma patientsTumor samplesPD-L1 mRNA expressionPD-L1 protein expressionOral tongue SCCCell carcinoma patientsOral tongue cancerImmune cell infiltrationPD-L1 mRNATumor immune microenvironmentNeck SCC cell linesNeck cancer cell linesSCC cell linesDevelopment of headCell linesCancer cell linesTongue SCCCarcinoma patientsNeurospora crassa is a potential source of anti-cancer agents against breast cancer
Han R, Yang H, Ling C, Lu L. Neurospora crassa is a potential source of anti-cancer agents against breast cancer. Breast Cancer 2022, 29: 1032-1041. PMID: 35881300, DOI: 10.1007/s12282-022-01383-9.Peer-Reviewed Original ResearchConceptsBreast cancerT-47DBreast cancer stem cellsBreast cancer cell linesBreast cancer invasivenessCancer stem cell-related genesStem cell-related genesTumor cell proliferationCancer stem cellsMouse model resultsAnti-tumor agentsCell-related genesAnti-cancer agentsCancer cell linesTumor growthCancer invasivenessCancer stemCell proliferationMCF-10ACell linesCancerInhibition rateStem cellsSpheroid formationCASP3 activityInvestigating Sources of Zeros in 10× Single-Cell RNAseq Data
Slowik H, Zyla J, Marczyk M. Investigating Sources of Zeros in 10× Single-Cell RNAseq Data. Lecture Notes In Computer Science 2022, 13347: 71-80. DOI: 10.1007/978-3-031-07802-6_6.Peer-Reviewed Original ResearchSingle-cell levelSingle-cell RNA sequencingSingle-cell RNAseq dataNumber of transcriptsMulti-omics dataGene expression estimatesRibosomal genesRNA sequencingExpression profilingEnrichment analysisRNAseq dataBiological pathwaysSequencing platformsExpression dataGenesExpression estimatesIndividual cellsBreast cancer cell linesCancer cell linesCell linesSingle experimentLow mappabilityTranscriptsSequencingProfilingGene expressions and their significance in organoid cultures obtained from breast cancer patient-derived biopsies
Pranav P, Palaniyandi T, Baskar G, Ravi M, Rajendran B, Sivaji A, Ranganathan M. Gene expressions and their significance in organoid cultures obtained from breast cancer patient-derived biopsies. Acta Histochemica 2022, 124: 151910. PMID: 35667159, DOI: 10.1016/j.acthis.2022.151910.Peer-Reviewed Original ResearchConceptsBreast cancerOrganoid culturesGene expression changesPatient-derived biopsiesBreast cancer biopsiesExpression of ErbB2Progesterone receptor geneCancer cell linesExpression changesSuch cancersPatient biopsiesCancer biopsiesSolid tumorsBiopsyMalignant cellsCancerGene expressionMagnitude of expressionHuman cancersCancer therapyReceptor geneCell linesSuch organoidsCancer researchFunctional physiology
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