2025
Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach
Lopez de Rodas M, Villalba-Esparza M, Sanmamed M, Chen L, Rimm D, Schalper K. Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach. Nature Reviews Clinical Oncology 2025, 22: 163-181. PMID: 39820025, DOI: 10.1038/s41571-024-00984-x.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesImmune-checkpoint inhibitorsTumor-infiltrating lymphocyte subpopulationsClinical significance of tumor-infiltrating lymphocytesPredictive value of tumor-infiltrating lymphocytesSignificance of tumor-infiltrating lymphocytesStudy of tumor-infiltrating lymphocytesImmune-checkpoint inhibitor therapyImmune-mediated tumor eliminationEra of immunotherapyT cell dysfunctionBiomarkers of responseSolid tumor typesImmunotherapeutic approachesAntigen-reactiveTumor microenvironmentTumor typesClinical outcomesTumor eliminationClinical significanceSingle-cell transcriptomicsPredictive valueAnticancer mechanismClinical implicationsResistance mechanismsHarnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition
Glaviano A, Lau H, Carter L, Lee E, Lam H, Okina E, Tan D, Tan W, Ang H, Carbone D, Yee M, Shanmugam M, Huang X, Sethi G, Tan T, Lim L, Huang R, Ungefroren H, Giovannetti E, Tang D, Bruno T, Luo P, Andersen M, Qian B, Ishihara J, Radisky D, Elias S, Yadav S, Kim M, Robert C, Diana P, Schalper K, Shi T, Merghoub T, Krebs S, Kusumbe A, Davids M, Brown J, Kumar A. Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition. Journal Of Hematology & Oncology 2025, 18: 6. PMID: 39806516, PMCID: PMC11733683, DOI: 10.1186/s13045-024-01634-6.Peer-Reviewed Original ResearchConceptsEpithelial-mesenchymal transitionTumor microenvironmentCancer progressionTherapeutic resistanceCancer therapyTumor microenvironment componentsTumor microenvironment modulationModulation of epithelial-mesenchymal transitionPromote tumor growthImprove treatment efficacyTumor microenvironment signalsTargeted cancer therapyTarget various componentsTherapeutic challengeTreatment responseTumor growthPromote metastasisTherapeutic strategiesTreatment efficacyEpithelial cellsMesenchymal traitsCancer cellsExtracellular matrix componentsCancerResistance mechanisms
2024
A brave new framework for glioma drug development
Hotchkiss K, Karschnia P, Schreck K, Geurts M, Cloughesy T, Huse J, Duke E, Lathia J, Ashley D, Nduom E, Long G, Singh K, Chalmers A, Ahluwalia M, Heimberger A, Bagley S, Todo T, Verhaak R, Kelly P, Hervey-Jumper S, de Groot J, Patel A, Fecci P, Parney I, Wykes V, Watts C, Burns T, Sanai N, Preusser M, Tonn J, Drummond K, Platten M, Das S, Tanner K, Vogelbaum M, Weller M, Whittle J, Berger M, Khasraw M. A brave new framework for glioma drug development. The Lancet Oncology 2024, 25: e512-e519. PMID: 39362262, DOI: 10.1016/s1470-2045(24)00190-6.Peer-Reviewed Original ResearchConceptsBrain tumorsBenefits of biopsyBrain tumor therapyLiquid biopsy technologiesTissue samplesPostoperative deficitsBiopsy techniqueBiopsy technologyEffective therapySurgical trialsClinical trialsTumor therapyResistance mechanismsTumorTherapyPatientsDrug developmentTissue analysisBrainTrialsTissueBiopsyGliomaRegulatory agenciesNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S, Griffin A, Karan C, Kerwin P, Murray D, Honig B, Liu Y, Califano A. Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis. Nature Communications 2024, 15: 3909. PMID: 38724493, PMCID: PMC11082183, DOI: 10.1038/s41467-024-47957-3.Peer-Reviewed Original ResearchConceptsMechanism of cell responseResistance mechanismsSignaling pathway responsesDrug resistance mechanismsEnzyme/substrate interactionsAdaptive resistance mechanismsNetwork rewiringPhosphorylation stateSignaling pathway activationDrug perturbationsProteomic technologiesSignaling crosstalkPathway responsesInhibitor designPathway activationCancer drug resistance mechanismsCell adaptive responsesAdaptive responsePhosphatase activityNetwork-based methodologyRewiringTherapeutic efficacyPhosphoproteome coverageCell responsesControl mediumBabesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies
Fang T, Mamoun C. Babesia duncani, a Model Organism for Investigating Intraerythrocytic Parasitism and Novel Antiparasitic Therapeutic Strategies. The Journal Of Infectious Diseases 2024, 230: 263-270. PMID: 39052743, PMCID: PMC11272067, DOI: 10.1093/infdis/jiae191.Peer-Reviewed Original ResearchConsequences of malariaDevelopment of future therapiesIntraerythrocytic parasitesHost red blood cellsDrugs in vitroB. duncaniIn vitro culture systemRed blood cellsFuture therapiesTherapeutic strategiesAnimal modelsWell-annotated genomeBlood cellsResistance mechanismsPathological consequencesMode of actionBabesia duncaniCulture systemParasite biologyPathogensMalariaPlasmodiumTherapyAnimalsCulture conditionsEpistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors
Hikichi Y, Grover J, Schäfer A, Mothes W, Freed E. Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors. Science Advances 2024, 10: eadn0042. PMID: 38427738, PMCID: PMC10906922, DOI: 10.1126/sciadv.adn0042.Peer-Reviewed Original ResearchConceptsIntegrase strand transfer inhibitorsClasses of antiretroviralsHuman immunodeficiency virusStrand transfer inhibitorsHIV-1Env mutationsTransfer inhibitorsIntegrase strand transfer inhibitor dolutegravirHIV-1 escapeResistance to dolutegravirResistance to antiretroviralsAbsence of resistance mutationsClasses of drugsCell-cell transferVirological failureImmunodeficiency virusResistance mutationsGene mutationsEnvelope glycoproteinAntiretroviralsEnvResistance mechanismsDolutegravirMutationsIntegrase
2023
Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru
Bickersmith S, Jurczynski J, Sallum M, Chaves L, Bergo E, Rodriguez G, Morante C, Rios C, Saavedra M, Alava F, Gamboa D, Vinetz J, Conn J. Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru. Genes 2023, 14: 1892. PMID: 37895241, PMCID: PMC10606710, DOI: 10.3390/genes14101892.Peer-Reviewed Original ResearchConceptsIndoor residual sprayMalaria endemic localitiesLow-intensity resistanceResistance mechanismsMalaria hotspotsCommon interventionInsecticidal netsMain resistance mechanismMalaria transmissionGenotypic detectionCodon 280Resistance mutationsEndemic localitiesPrimary malaria vectorVoltage-gated sodium channel geneResidual spraySodium channel geneChannel genesNon-synonymous mutationsACEPresent studyMalaria vectorsInterventionMutationsS6 segmentLeveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies
Anderson K, Braun D, Buqué A, Gitto S, Guerriero J, Horton B, Keenan B, Kim T, Overacre-Delgoffe A, Ruella M, Triplett T, Veeranki O, Verma V, Zhang F. Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies. Journal For ImmunoTherapy Of Cancer 2023, 11: e006533. PMID: 37399356, PMCID: PMC10314654, DOI: 10.1136/jitc-2022-006533.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsImmune resistance mechanismsImmune resistanceChimeric antigen receptor T cellsAntigen receptor T cellsImmune checkpoint inhibitorsReceptor T cellsVariety of malignanciesNew therapeutic strategiesResistance mechanismsCheckpoint inhibitorsDurable responsesMost patientsAnticancer immunotherapyTherapy combinationsCurrent therapiesT cellsIndividual patientsSolid cancersTherapeutic strategiesTumor profilingPatientsOverall efficacySuppressive mechanismsBispecific antibodiesTumor microenvironmentImmune Resistance Mechanisms and the Road to Personalized Immunotherapy.
Piper M, Kluger H, Ruppin E, Hu-Lieskovan S. Immune Resistance Mechanisms and the Road to Personalized Immunotherapy. American Society Of Clinical Oncology Educational Book 2023, 43: e390290. PMID: 37459578, DOI: 10.1200/edbk_390290.Peer-Reviewed Original ResearchCirculating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma
Berko E, Witek G, Matkar S, Petrova Z, Wu M, Smith C, Daniels A, Kalna J, Kennedy A, Gostuski I, Casey C, Krytska K, Gerelus M, Pavlick D, Ghazarian S, Park J, Marachelian A, Maris J, Goldsmith K, Radhakrishnan R, Lemmon M, Mossé Y. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Nature Communications 2023, 14: 2601. PMID: 37147298, PMCID: PMC10163008, DOI: 10.1038/s41467-023-38195-0.Peer-Reviewed Original ResearchConceptsAnaplastic lymphoma kinaseLorlatinib resistanceTumor DNAPhase 1 trialCirculating tumor DNAPre-clinical studiesResistance mechanismsTumor DNA samplesALK mutationsDisease progressionHeterogeneity of tumorsClinical utilityRAS-MAPK pathwayTherapeutic strategiesLymphoma kinasePatientsResistance mutationsNeuroblastomaProgressionTrialsMutationsBiochemical assaysDNA samplesPoint mutationsLorlatinibBedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis
Sonnenkalb L, Carter J, Spitaleri A, Iqbal Z, Hunt M, Malone K, Utpatel C, Cirillo D, Rodrigues C, Nilgiriwala K, Fowler P, Merker M, Niemann S, Consortium C, Barilar I, Battaglia S, Borroni E, Brandao A, Brankin A, Cabibbe A, Carter J, Cirillo D, Claxton P, Clifton D, Cohen T, Coronel J, Crook D, Dreyer V, Earle S, Escuyer V, Ferrazoli L, Fowler P, Gao G, Gardy J, Gharbia S, Ghisi K, Ghodousi A, Cruz A, Grandjean L, Grazian C, Groenheit R, Guthrie J, He W, Hoffmann H, Hoosdally S, Hunt M, Iqbal Z, Ismail N, Jarrett L, Joseph L, Jou R, Kambli P, Khot R, Knaggs J, Koch A, Kohlerschmidt D, Kouchaki S, Lachapelle A, Lalvani A, Lapierre S, Laurenson I, Letcher B, Lin W, Liu C, Liu D, Malone K, Mandal A, Mansjö M, Matias D, Meintjes G, de Freitas Mendes F, Merker M, Mihalic M, Millard J, Miotto P, Mistry N, Moore D, Musser K, Ngcamu D, Hoang N, Niemann S, Nilgiriwala K, Nimmo C, Okozi N, Oliveira R, Omar S, Paton N, Peto T, Pinhata J, Plesnik S, Puyen Z, Rabodoarivelo M, Rakotosamimanana N, Rancoita P, Rathod P, Rodger G, Rodrigues C, Rodwell T, Roohi E, Santos-Lazaro D, Shah S, Kohl T, Smith G, Solano W, Spitaleri A, Supply P, Surve U, Tahseen S, Thuong N, Thwaites G, Todt K, Trovato A, Utpatel C, Van Rie A, Vijay S, Walker T, Walker S, Warren R, Werngren J, Wijkander M, Wilkinson R, Wilson D, Wintringer P, Yu X, Yang Y, Zhao Y, Yao S, Zhu B. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis. The Lancet Microbe 2023, 4: e358-e368. PMID: 37003285, PMCID: PMC10156607, DOI: 10.1016/s2666-5247(23)00002-2.Peer-Reviewed Original ResearchConceptsMutation catalogueIn silico data analysisBedaquiline resistanceClofazimine resistanceResistance mechanismsProtein modelsClinical Mycobacterium tuberculosis complex isolatesImpaired DNA bindingClinically resistant strainsMinimum inhibitory concentrationVariants in vitroPacBio sequencingGenome sequenceGenomic rearrangementsGenomic variantsIn vitroExperimental evolutionGenotype dataTranscriptional repressorDrug resistance mechanismsClinical isolatesPhenotypic dataResistance determinantsDNA bindingProtein dimerisation
2022
The current state of the art and future trends in RAS-targeted cancer therapies
Punekar S, Velcheti V, Neel B, Wong K. The current state of the art and future trends in RAS-targeted cancer therapies. Nature Reviews Clinical Oncology 2022, 19: 637-655. PMID: 36028717, PMCID: PMC9412785, DOI: 10.1038/s41571-022-00671-9.Peer-Reviewed Original ResearchConceptsDuration of responseNovel combination therapiesCombination therapyClinical trialsTherapeutic strategiesSolid tumorsMutant KRASTumor microenvironmentDrug resistanceRAS pathwayCancer cellsDevelopment of inhibitorsCancer therapyOncogenic RASPatientsOncogenic proteinsTherapyKRASResistance mechanismsMutant isoformsInhibitorsRASMalignancyTumorsCancerClassic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome
Cox ZL, Rao VS, Testani JM. Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome. Kidney360 2022, 3: 954-967. PMID: 36128483, PMCID: PMC9438407, DOI: 10.34067/kid.0006372021.Commentaries, Editorials and LettersConceptsCardiorenal syndromeDiuretic resistanceSodium avidityAcute decompensated heart failureDecompensated heart failureRenal sodium avidityHeart failure phenotypeResistance mechanismsDiuretic therapyHeart failureFailure populationNovel mechanismMultiple etiologiesGlomerular filtrationTherapeutic strategiesFailure phenotypeSyndromeTranslate findingsAviditySpecific transportersTherapyEtiologyPopulationRecent literatureResistance Mechanisms to Anti-PD Cancer Immunotherapy
Vesely MD, Zhang T, Chen L. Resistance Mechanisms to Anti-PD Cancer Immunotherapy. Annual Review Of Immunology 2022, 40: 45-74. PMID: 35471840, DOI: 10.1146/annurev-immunol-070621-030155.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnti-PD therapyCancer immunotherapyMechanisms of resistanceImmune inhibitory moleculesFraction of patientsResistance mechanismsNormalization cancer immunotherapyAdditional immunotherapyPD-1Clinical evidenceAntigen presentationT cellsSolid tumorsTherapy resistanceH1 pathwayTumor microenvironmentImmunotherapyInhibitory moleculesHematopoietic malignanciesCancer treatmentTherapyPatientsCurrent studyCancer dataMalignancy
2021
A review of FLT3 inhibitors in acute myeloid leukemia
Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Reviews 2021, 52: 100905. PMID: 34774343, PMCID: PMC9846716, DOI: 10.1016/j.blre.2021.100905.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaFLT3 mutationsMyeloid leukemiaTreatment of AMLInhibitor maintenance therapyDrug resistance mechanismsCommon genetic aberrationsConsolidation chemotherapyRefractory FLT3Maintenance therapyPoor prognosisPrognostic implicationsStromal protectionFLT3 inhibitorsStandard inductionADMIRAL studyFLT3Genetic aberrationsLeukemiaResistance mechanismsMutationsMonotherapyChemotherapyPrognosisGilteritinibMS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling
Xin S, Mueller C, Pfeiffer S, Kraft V, Merl-Pham J, Bao X, Feederle R, Jin X, Hauck S, Schmitt-Kopplin P, Schick J. MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling. Cell Death & Differentiation 2021, 29: 670-686. PMID: 34663908, PMCID: PMC8901757, DOI: 10.1038/s41418-021-00883-z.Peer-Reviewed Original ResearchConceptsCell deathDiverse cellular processesLipid droplet dispersionIron-dependent formKey resistance mechanismNovel tetraspaninCellular processesLipid remodelingFerroptosis resistanceLuminal Ca2Endoplasmic reticulumCellular lipidsCell survivalLipid reservoirsDetoxification pathwaysCancer cell linesLipid elongationBiochemical processesMembrane phospholipidsEther lipidsResistance mechanismsCell linesFerroptosisLipid compartmentsSpeciesOsimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance
Talsania A, Zhang J, Wilson F. Osimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance. Current Cancer Research 2021, 65-73. DOI: 10.1007/978-3-030-74028-3_4.ChaptersNon-small cell lung carcinomaEGFR-mutant non-small cell lung carcinomaEpidermal growth factor receptorCell lung carcinomaLung carcinomaSmall cell lung carcinomaEGFR-Mutant NonMajor therapeutic challengeCare of patientsPotential therapeutic strategyConstitutive EGFR activationThird-generation EGFR inhibitorsUpregulation of pathwaysGrowth factor receptorResistance mechanismsAdjuvant settingTherapeutic challengeMechanisms of resistanceClinical activityTherapeutic strategiesClinical developmentSmall molecule inhibitorsEGFR inhibitorsFactor receptorEGFR activationResistance mechanisms to checkpoint inhibitors
Weiss SA, Sznol M. Resistance mechanisms to checkpoint inhibitors. Current Opinion In Immunology 2021, 69: 47-55. PMID: 33676271, DOI: 10.1016/j.coi.2021.02.001.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-1/PD-L1 axisMultiple immune checkpoint inhibitorsPD1/PD-L1PD-L1 axisHuman translational studiesPre-clinical studiesPre-clinical animalResistance mechanismsCheckpoint inhibitorsPD-L1Clinical outcomesTreatment failureClinical trialsTranslational studiesCancer treatmentPotential mechanismsInhibitorsPatientsClinicTrialsAntibodies
2020
Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells
Marczyk M, Patwardhan GA, Zhao J, Qu R, Li X, Wali VB, Gupta AK, Pillai MM, Kluger Y, Yan Q, Hatzis C, Pusztai L, Gunasekharan V. Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells. Cancers 2020, 12: 2551. PMID: 32911681, PMCID: PMC7563413, DOI: 10.3390/cancers12092551.Peer-Reviewed Original ResearchTriple-negative breast cancer cellsCancer cellsBreast cancer cellsStress response genesMulti-omics landscapeCell population compositionDrug-induced cell deathMulti-omics investigationsCell linesBCL2 family inhibitorsSingle-cell analysisChromatin accessibilityGenome structureMDA-MB-231 triple-negative breast cancer cellsChromatin structureMethylation stateResponse genesFamily inhibitorsCell deathTNBC cell linesNumber variationsDefense mechanismsResistance mechanismsNew therapeutic strategiesGenesMolecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?
Savic LJ, Doemel LA, Schobert IT, Montgomery RR, Joshi N, Walsh JJ, Santana J, Pekurovsky V, Zhang X, Lin M, Adam L, Boustani A, Duncan J, Leng L, Bucala RJ, Goldberg SN, Hyder F, Coman D, Chapiro J. Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy? Radiology 2020, 296: 575-583. PMID: 32633675, PMCID: PMC7434651, DOI: 10.1148/radiol.2020200373.Peer-Reviewed Original ResearchConceptsImmuno-oncologic therapiesConventional transarterial chemoembolizationTransarterial chemoembolizationIntratumoral immune cell infiltrationMR spectroscopyRabbit liver tumor modelPrussian blue iron stainingAntigen-presenting immune cellsIntra-arterial infusionImmune cell infiltrationNew Zealand white rabbitsLiver tumor modelImmune cell exclusionLiver cancer modelContrast material administrationT2-weighted MRIZealand white rabbitsT2-weighted imagingResistance mechanismsImmunosuppressive tumorHLA-DRCell infiltrationImmune cellsImmunohistochemistry stainingRing enhancement
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