2024
A novel sensitizer reduces EGFR-TKI resistance by regulating the PI3K/Akt/mTOR pathway and autophagy
Zhang J, Qu Z, Xiao X, Adelson D, Wang F, Wei A, Harata-Lee Y, Cui J, He D, Xie L, Sun L, Li J, Huang Z, Aung T, Yao H, Lin L. A novel sensitizer reduces EGFR-TKI resistance by regulating the PI3K/Akt/mTOR pathway and autophagy. Heliyon 2024, 11: e41104. PMID: 39844968, PMCID: PMC11750466, DOI: 10.1016/j.heliyon.2024.e41104.Peer-Reviewed Original ResearchEpidermal growth factor receptor tyrosine kinase inhibitorsEGFR-TKI-resistant cell linesNon-small cell lung cancerInhibition of drug resistanceLung cancerEpidermal growth factor receptor tyrosine kinase inhibitor resistanceDrug resistanceGrowth factor receptor tyrosine kinase inhibitorsCell linesReceptor tyrosine kinase inhibitorsEGFR-TKI resistanceResistance to gefitinibCell lung cancerFirst-line treatmentPI3K/AKT/mTOR pathwayMortality of lung cancerEGFR mutationsTreatment failureMolecular mechanismsDose-dependentlyKinase inhibitorsFlow cytometryAnticancer effectsGefitinibH1650 cellsUnilateral focal palmoplantar keratoderma associated with a postzygotic variant in PIK3CA and activation of the PI3K/AKT/mTOR pathway.
Gong Z, Peng S, Wang H, Jiang X, Ke X, Lin Z. Unilateral focal palmoplantar keratoderma associated with a postzygotic variant in PIK3CA and activation of the PI3K/AKT/mTOR pathway. European Journal Of Dermatology 2024, 34: 287-293. PMID: 39015962, DOI: 10.1684/ejd.2024.4704.Peer-Reviewed Original ResearchConceptsFocal palmoplantar keratodermaLaser capture microdissectionIdentified missense variantsPalmoplantar keratodermaWhole-exome sequencingMissense variantsGenomic DNASomatic variantsGenetic basisSanger sequencingMolecular dockingPostzygotic variantsBiological processesPI3K/AKT/mTOR pathwayPhenotypic heterogeneityEpidermal nevusPatient's peripheral bloodCongenital overgrowth disorderVariantsPIK3CASequencePeripheral bloodPI3K/Akt/mTOR signalingAffected epidermisOvergrowth disorder
2023
PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.
Exposito F, Redrado M, Houry M, Hastings K, Molero-Abraham M, Lozano T, Solorzano J, Sanz-Ortega J, Adradas V, Amat R, Redin E, Leon S, Legarra N, Garcia J, Serrano D, Valencia K, Robles-Oteiza C, Foggetti G, Otegui N, Felip E, Lasarte J, Paz-Ares L, Zugazagoitia J, Politi K, Montuenga L, Calvo A. PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells. Cancer Research 2023, 83: 2513-2526. PMID: 37311042, DOI: 10.1158/0008-5472.can-22-3023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLung squamous carcinomaAnti-PD-1 therapyRegulatory T cellsCell lung cancerImmunosuppressive microenvironmentLung cancerImmunotherapy resistanceT cellsWorse progression-free survivalCell death protein 1PTEN lossAnti-TGFβ antibodyConversion of CD4PI3K/AKT/mTOR pathwayProgression-free survivalDeath protein 1Treatment of miceImmunosuppressive tumor microenvironmentPTEN/PI3K/AKT/mTOR pathwayAKT/mTOR pathwayPD-L1TLR agonistsTumor rejectionSquamous carcinoma
2022
A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma
Sun R, Liu Y, Lei C, Tang Z, Lu L. A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma. Biological Procedures Online 2022, 24: 7. PMID: 35751033, PMCID: PMC9233353, DOI: 10.1186/s12575-022-00170-2.Peer-Reviewed Original ResearchCutaneous melanomaLack of therapeutic optionsPrediction of prognosisHigh-risk groupBackgroundThe prognosisMalignancy of cancerTherapeutic optionsTherapeutic responseClinical factorsPrognosisCellular proliferationClinical practicePatientsPI3K/AKT/mTOR pathwayTCGA databaseMelanomaUp-regulatedFunctional analysisPotential drug targetsMolecular mechanismsBioinformatic evidenceDrug targetsRNA splicing
2019
PLEKHA5 regulates tumor growth in metastatic melanoma
Zhang H, Zhu H, Deng G, Zito CR, Oria VO, Rane CK, Zhang S, Weiss SA, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg MW, Kluger HM, Jilaveanu LB. PLEKHA5 regulates tumor growth in metastatic melanoma. Cancer 2019, 126: 1016-1030. PMID: 31769872, PMCID: PMC7147081, DOI: 10.1002/cncr.32611.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsApoptosis Regulatory ProteinsBiomarkers, TumorBrain NeoplasmsCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, NudeMiddle AgedPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesTumor Cells, CulturedXenograft Model Antitumor AssaysYoung AdultConceptsTumor growthDisseminated melanomaExtracranial melanoma metastasesPI3K/AKT/mTOR pathwayMelanoma brain metastasesBetter overall survivalPI3K/Akt/mTORAKT/mTOR pathwayCell proliferationAkt/mTORMelanoma xenograft modelGrowth of tumorsS cell cycle transitionBrain metastasesOverall survivalPoor prognosisMetastatic melanomaMAPK/ERKSubcutaneous inoculationMelanoma metastasesXenograft modelClinical relevanceMelanoma growthNude miceCerebral specimensWhole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsAn effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer
Zhang J, Qu Z, Yao H, Sun L, Harata-Lee Y, Cui J, Aung TN, Liu X, You R, Wang W, Hai L, Adelson DL, Lin L. An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer. Biomedicine & Pharmacotherapy 2019, 118: 109169. PMID: 31310954, DOI: 10.1016/j.biopha.2019.109169.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsAutophagyCarcinoma, Non-Small-Cell LungCell Line, TumorCell SurvivalDown-RegulationDrug Resistance, NeoplasmDrugs, Chinese HerbalGefitinibGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesUp-RegulationConceptsNon-small cell lung cancerCompound Kushen InjectionPI3K/AKT/mTOR pathwayCell lung cancerAKT/mTOR pathwayLung cancerGefitinib treatmentMTOR pathwayFirst-line treatment optionDrug sensitivityPositive EGFR mutationDose-dependent fashionSensitive cell linesMost patientsTreatment optionsEGFR mutationsKushen InjectionTreatment relapseSensitizing agentGefitinibCancerRegulation of autophagyDown regulationTreatment effectsPatientsPI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers
Bonazzoli E, Cocco E, Lopez S, Bellone S, Zammataro L, Bianchi A, Manzano A, Yadav G, Manara P, Perrone E, Haines K, Espinal M, Dugan K, Menderes G, Altwerger G, Han C, Zeybek B, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers. Gynecologic Oncology 2019, 153: 158-164. PMID: 30630630, PMCID: PMC6430698, DOI: 10.1016/j.ygyno.2019.01.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesClass Ia Phosphatidylinositol 3-KinaseDrug Resistance, NeoplasmFemaleGenital Neoplasms, FemaleHumansMiceMice, SCIDMiddle AgedMutationPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsReceptor, ErbB-2TransfectionXenograft Model Antitumor AssaysConceptsHER2/neuAKT/mTOR pathwayPIK3CA mutationsMTOR pathwayActivity of afatinibEffect of afatinibPI3K/AKT/mTOR pathwayPotential mechanismsPIK3CA/AKT/mTOR pathwayRapid tumor growthGreater compensatory increasePI3K mutationsAmplification/mutationOncogenic PIK3CA mutationsAfatinib exposurePIK3CA H1047RGynecological cancerClinical trialsMTOR inhibitorsAfatinibTumor growthCompensatory increasePhosphorylated Akt proteinPIK3CA geneC-erb
2017
Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells
Kim S, Son K, Kim K, Yu S, Park S, Kim Y, Nam H, Suh J, Ji J, Ahn S. Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells. Pharmacological Reports 2017, 69: 878-884. PMID: 28623712, DOI: 10.1016/j.pharep.2017.04.007.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, PhytogenicApoptosisAutophagyBone NeoplasmsCell Line, TumorCell SurvivalDrugs, Chinese HerbalGene Expression RegulationHumansOsteosarcomaPhosphoinositide-3 Kinase InhibitorsPodophyllotoxinProto-Oncogene Proteins c-aktReactive Oxygen SpeciesTOR Serine-Threonine KinasesConceptsReactive oxygen speciesPI3K/AKT/mTOR pathwayAKT/mTOR pathwayU2OS cellsAcidic vesicular organelles (AVOs) formationMTOR pathwayMitochondrial reactive oxygen speciesOsteosarcoma U2OS cellsCell death modeOxygen speciesPropidium iodidePI3K/Akt/mTORCell cycle arrestLight chain 3Cell viabilityCellular processesInhibition of apoptosisAkt/mTOROrganelle formationAcridine orange stainingAutophagy processApoptotic responseDeath modeWestern blot analysisCell survival
2015
Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury
Zou Y, Stagi M, Wang X, Yigitkanli K, Siegel CS, Nakatsu F, Cafferty WB, Strittmatter SM. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury. Journal Of Neuroscience 2015, 35: 10429-10439. PMID: 26203138, PMCID: PMC4510284, DOI: 10.1523/jneurosci.1718-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalGene Knockdown TechniquesImmunohistochemistryInositol Polyphosphate 5-PhosphatasesMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationPhosphoric Monoester HydrolasesRecovery of FunctionReverse Transcriptase Polymerase Chain ReactionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryEndogenous suppressorAxon regenerationNonoverlapping substrate specificityGenome-wide scaleHigh-throughput functional screensFunctional recoveryAxonal regenerationCNS axon repairSpinal cord injury researchDorsal hemisection injuryMammalian genesPI3K/AKT/mTOR pathwayCNS axon growthAKT/mTOR pathwayLipid phosphataseCorticospinal tract axonsCNS axon regenerationAdult mammalian CNSFunctional screenSubstrate specificityNovel suppressorShRNA resultsINPP5F
2014
Pancreatic neuroendocrine tumors: Pathologic and molecular characteristics
Shi C, Klimstra D. Pancreatic neuroendocrine tumors: Pathologic and molecular characteristics. Seminars In Diagnostic Pathology 2014, 31: 498-511. PMID: 25441311, DOI: 10.1053/j.semdp.2014.08.008.Peer-Reviewed Original ResearchConceptsNeuroendocrine tumorsNeuroendocrine carcinomaWell-differentiated neuroendocrine tumorsPancreatic well-differentiated neuroendocrine tumorPancreatic neuroendocrine tumorsMolecular targeted therapyPancreatic neuroendocrine neoplasmsPancreatic neuroendocrine tumorigenesisNeuroendocrine neoplasmsNeuroendocrine tumorigenesisTumorPI3K/AKT/mTOR pathwayCarcinomaMolecular mechanismsChromatin remodelingNeoplasmsTP53TherapyPatientsOpen-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †
Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do K, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †. Annals Of Oncology 2014, 25: 1122-1127. PMID: 24669015, PMCID: PMC4037860, DOI: 10.1093/annonc/mdu124.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathological complete responseStandard neoadjuvant chemotherapyNeoadjuvant chemotherapyReverse phase protein arrayBreast cancerPrimary triple-negative breast cancerMTOR pathwayReceptor-negative breast cancerTriple receptor-negative breast cancerAddition of everolimusGrade 3 pneumonitisGrade 3/4 stomatitisPI3K/AKT/mTOR pathwayRash/desquamationClinical response rateGrade 3/4 toxicitiesPhase II studyClinical end pointsCombination of paclitaxelAKT/mTOR pathwayDirect antiproliferative activityBreast cancer cellsDownregulation of mTORII study
2013
The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross‐talk, and therapies
Vander Broek R, Mohan S, Eytan D, Chen Z, Van Waes C. The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross‐talk, and therapies. Oral Diseases 2013, 21: 815-825. PMID: 24219320, DOI: 10.1111/odi.12206.Peer-Reviewed Original ResearchConceptsAkt/mTOR axisPI3K/Akt/mTOR axisDNA copy number variationsMTOR axisCopy number variationsPI3K/Akt/mTORDysregulation of mRNAsNeck squamous cell carcinomaPI3K/AKT/mTOR pathwayAKT/mTOR pathwayAkt/mTORSquamous cell carcinomaPathway leadCell survivalNumber variationsPI3KMalignant phenotypeMTOR pathwayNormal physiologyCell carcinomaHNSCC casesNeck cancerClinical studiesProtein expressionGenetic aberrations
2012
A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer.
Krop I, Saura C, Rodon Ahnert J, Becerra C, Britten C, Isakoff S, Demanse D, Hackl W, Quadt C, Silva A, Burris H, Abu-Khalaf M, Baselga J. A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer. Journal Of Clinical Oncology 2012, 30: 508-508. DOI: 10.1200/jco.2012.30.15_suppl.508.Peer-Reviewed Original ResearchMetastatic breast cancerPI3K pathway alterationsBreast cancerG3 nauseaResistant HER2Disease stabilizationPathway alterationsPI3K/AKT/mTOR pathwayAcceptable safety profileDose-escalation studyAdvanced solid tumorsAKT/mTOR pathwayBreast cancer modelLogistic regression modelsPI3K pathwayG3 fatigueObserved DLTsBrain metastasesPartial responseSkin rashAdverse eventsLiver metastasesDose escalationSafety profileDose levelsMulti-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cellsHeat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors.
Gloesenkamp C, Nitzsche B, Lim A, Normant E, Vosburgh E, Schrader M, Ocker M, Scherübl H, Höpfner M. Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors. International Journal Of Oncology 2012, 40: 1659-67. PMID: 22246317, DOI: 10.3892/ijo.2012.1328.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzoquinonesCell Cycle CheckpointsCell Line, TumorCell MovementCell ProliferationChick EmbryoChorioallantoic MembraneDose-Response Relationship, DrugFlow CytometryGastrointestinal NeoplasmsGene Expression ProfilingGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansLactams, MacrocyclicNeuroendocrine TumorsPhosphatidylinositol 3-KinaseProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptor, IGF Type 1Signal TransductionTOR Serine-Threonine KinasesConceptsShock protein 90IGF-1 receptorIPI-504Protein 90GEP-NETsNeuroendocrine tumorsHsp90 inhibitor IPI-504Heat shock protein 90Antiproliferative effectsGEP-NET cellsDose-dependent growth inhibitionGEP-NET treatmentPI3K/AKT/mTOR pathwayGastrointestinal neuroendocrine tumorsGastroenteropancreatic neuroendocrine tumorsAKT/mTOR pathwayCancer gene expressionAdditive antiproliferative effectsCell cycle arrestInnovative therapeutic approachesTyrosine kinase inhibitionGrowth inhibitionMechanism of actionGene expressionHsp90 inhibition
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply