2025
SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer
Jiang Z, Bi F, Ge Z, Mansolf M, Hartwich T, Kolesnyk V, Yang K, Park W, Kim D, Grechukhina O, Hui P, Kim S, Yang-Hartwich Y. SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer. Cancers 2025, 17: 244. PMID: 39858026, PMCID: PMC11763764, DOI: 10.3390/cancers17020244.Peer-Reviewed Original ResearchEpidermal growth factor receptorOvarian cancerRecurrent tumorsSortilin-related receptor 1Therapeutic efficacy of carboplatinResistant to conventional chemotherapyResistant ovarian cancerMolecular mechanisms of chemoresistanceCancer models in vitroEfficacy of carboplatinRecurrent ovarian cancerOvarian cancer treatmentEffective targeted therapiesMechanisms of chemoresistancePro-tumor functionsGrowth factor receptorXenograft mouse modelConventional chemotherapyStabilization of epidermal growth factor receptorModel in vitroPro-tumorEnhanced chemoresistanceCarboplatin resistanceTherapeutic efficacyFactor receptor
2024
Comparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups
Olkowski C, Basuli F, Fernandes B, Ghaemi B, Shi J, Zhang H, Farber J, Escorcia F, Choyke P, Jacobson O. Comparative Kidney Uptake of Nanobody-Based PET Tracers Labeled with Various Fluorine-18-Labeled Prosthetic Groups. Molecular Pharmaceutics 2024, 22: 533-543. PMID: 39680709, DOI: 10.1021/acs.molpharmaceut.4c01101.Peer-Reviewed Original ResearchA Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer
Jia J, Moyer A, Lowe M, Bolch E, Kortmansky J, Cho M, Lenz H, Kalyan A, Niedzwiecki D, Strickler J. A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. Journal Of Gastrointestinal Cancer 2024, 56: 29. PMID: 39652198, DOI: 10.1007/s12029-024-01156-x.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsMetastatic colorectal cancerPhase 2 studyEpidermal growth factor receptorAnti-tumor activityStable diseaseProgressive diseaseChemotherapy refractory metastatic colorectal cancerOral small-molecule tyrosine kinase inhibitorColorectal cancerResistance to epidermal growth factor receptorSmall molecule tyrosine kinase inhibitorsRefractory metastatic colorectal cancerBest overall responseRAS wild-typeAdvanced solid tumorsBiomarker-selected patientsTyrosine kinase inhibitorsWild-typeGrowth factor receptorResultsFive patientsPrimary endpointSecondary endpointsSolid tumorsSavolitinibThe evolving landscape of adjuvant therapy in T1-T2N0 resected non-small cell lung cancer: a narrative review
Zolfaghari E, Dhanasopon A, Woodard G. The evolving landscape of adjuvant therapy in T1-T2N0 resected non-small cell lung cancer: a narrative review. Journal Of Thoracic Disease 2024, 0: 0-0. PMID: 39831209, PMCID: PMC11740046, DOI: 10.21037/jtd-24-245.Peer-Reviewed Original ResearchNon-small cell lung cancerEpidermal growth factor receptorEarly-stage non-small cell lung cancerAnaplastic lymphoma kinaseAdjuvant therapyCell lung cancerEarly-stage patientsSurgical resectionOverall survivalAdjuvant chemotherapyLung cancerSurvival benefit of adjuvant therapyAdjuvant platinum-based chemotherapyBenefit of adjuvant therapyHigh-risk pathologic featuresStage IB tumorsNational Clinical Trials RegistryPlatinum-based chemotherapyHigh-risk featuresCirculating tumor DNALandscape of adjuvant therapyLung cancer recurrenceGrowth factor receptorClinical Trials RegistryAdjuvant osimertinibTreatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib
Robinson N, Canavan M, Zhan P, Udelsman B, Pathak R, Boffa D, Goldberg S. Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib. Clinical Lung Cancer 2024, 26: 9-17.e3. PMID: 39462746, DOI: 10.1016/j.cllc.2024.09.006.Peer-Reviewed Original ResearchNon-small cell lung cancerEGFR-mutant non-small cell lung cancerFirst-line osimertinibContinuation of osimertinibImmune checkpoint inhibitorsTyrosine kinase inhibitorsCell lung cancerRetrospective cohort studyOverall survivalTreatment regimensLung cancerAdvanced epidermal growth factor receptorAssociated with increased PFSAssociated with superior PFSSecond-line treatment regimenEGFR exon 19 deletionRetrospective cohort study of patientsEGFR tyrosine kinase inhibitorsAssociated with prolonged survivalCohort study of patientsSecond-line treatment regimensExon 19 deletionFirst-line therapyEpidermal growth factor receptorFirst-line treatmentTislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study
Xu X, Ai L, Hu K, Liang L, Lv M, Wang Y, Cui Y, Li W, Li Q, Yu S, Feng Y, Liu Q, Yang Y, Zhang J, Xu F, Yu Y, Liu T. Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study. Nature Communications 2024, 15: 7255. PMID: 39179622, PMCID: PMC11343749, DOI: 10.1038/s41467-024-51536-x.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerVariant allele frequencyPhase 2 studyEpidermal growth factor receptorAdverse eventsRAS wild-type metastatic colorectal cancerRAS wt metastatic colorectal cancerSingle-arm phase 2 studyWild-type metastatic colorectal cancerColorectal cancerTreatment-related adverse eventsAnti-PD-1Disease control rateProgression-free survivalRAS wild-typeTumor immune responseCombined treatment regimenWild-typeGrowth factor receptorIrinotecan combinationOverall survivalAnti-EGFRPrimary endpointTumor DNASingle-armChitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer
Kamle S, Ma B, Schor G, Bailey M, Pham B, Cho I, Khan H, Azzoli C, Hofstetter M, Sadanaga T, Herbst R, Politi K, Lee C, Elias J. Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer. Translational Oncology 2024, 49: 102108. PMID: 39178575, PMCID: PMC11388375, DOI: 10.1016/j.tranon.2024.102108.Peer-Reviewed Original ResearchNon-small cell lung cancerEpidermal growth factor receptorTyrosine kinase inhibitorsEpidermal growth factor receptor mutant non-small cell lung cancerMutant non-small cell lung cancerEpidermal growth factor receptor axisCell lung cancerLung cancerTherapeutic resistanceDownstream targets of EGFRResistance to TKI therapyEpithelial cellsStimulated epidermal growth factor receptorWild type epidermal growth factor receptorTargeting of epidermal growth factor receptorActivating EGFR mutationsChitinase 3-like 1Progression free survivalInduce tumor cell deathEpidermal growth factor receptor activationEffects of EGFR activationInhibited pulmonary metastasisTumor cell deathResponse to treatmentGrowth factor receptor566 Staphylococcus epidermidis for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity
Mootien S, Leger R, Whitfill T. 566 Staphylococcus epidermidis for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity. Journal Of Investigative Dermatology 2024, 144: s99. DOI: 10.1016/j.jid.2024.06.582.Peer-Reviewed Original ResearchTyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)
Pike L, Miao E, Boe L, Patil T, Imber B, Myall N, Pollom E, Hui C, Qu V, Langston J, Chiang V, Grant M, Goldberg S, Palmer J, Prasad R, Wang T, Lee A, Shu C, Chen L, Thomas N, Braunstein S, Kavanagh B, Camidge D, Rusthoven C. Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC). Journal Of Clinical Oncology 2024, 42: 3606-3617. PMID: 39047224, PMCID: PMC11874932, DOI: 10.1200/jco.23.02668.Peer-Reviewed Original ResearchNon-small cell lung cancerUp-front stereotactic radiosurgeryTyrosine kinase inhibitorsALK-driven NSCLCStereotactic radiosurgeryBrain metastasesCell lung cancerOverall survivalCNS controlLung cancerOncogene-driven non-small cell lung cancerKinase inhibitorsCNS progression-free survivalStereotactic radiosurgery groupTKI-naive patientsProgression-free survivalAnaplastic lymphoma kinaseEpidermal growth factor receptorCox proportional hazards modelsGrowth factor receptorClinically relevant factorsProportional hazards modelMedian OSNo significant differenceNeurological symptomsImmune Cell Dynamics in EGFR-Mutated NSCLC Treated With Afatinib and Pembrolizumab: Results From a Phase IB Study
Riess J, Lara M, de Rodas M, Luxardi G, Herbert S, Shimoda M, Kelly K, Meerlev A, Moore E, Beckett L, Monjazeb A, Schalper K, Maverakis E, Gandara D. Immune Cell Dynamics in EGFR-Mutated NSCLC Treated With Afatinib and Pembrolizumab: Results From a Phase IB Study. JTO Clinical And Research Reports 2024, 5: 100706. PMID: 39318388, PMCID: PMC11420451, DOI: 10.1016/j.jtocrr.2024.100706.Peer-Reviewed Original ResearchImmune related adverse eventsNon-small cell lung cancerEGFR-mutant non-small cell lung cancerMaximum tolerated doseEpidermal growth factor receptorImmune cell subsetsT cellsEGFR-TKIsCell subsetsPD-1 antibody pembrolizumabRecommended phase 2 doseCentral memory T cellsAssociated with anti-tumor activityCD8+ T cellsCD3+ T cellsEGFR-TKI afatinibPD-(L)1 blockadePhase 2 doseTreated with afatinibPhase Ib studyMemory T cellsImmune cell dynamicsControlling brain metastasesCell lung cancerCD4/CD8 T cellsStructural insights into the role and targeting of EGFRvIII
Bagchi A, Stayrook S, Xenaki K, Starbird C, Doulkeridou S, El Khoulati R, Roovers R, Schmitz K, van Bergen En Henegouwen P, Ferguson K. Structural insights into the role and targeting of EGFRvIII. Structure 2024, 32: 1367-1380.e6. PMID: 38908376, PMCID: PMC11380598, DOI: 10.1016/j.str.2024.05.018.Peer-Reviewed Original ResearchKROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.
Gregorc V, González-Cao M, Salvagni S, Koumarianou A, Gil-Bazo I, Maio M, Viteri S, Majem M, Gutiérrez V, Bernabe Caro R, Sanmamed M, Zhu H, Shen H, Wang Y, Rosell R. KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC. Journal Of Clinical Oncology 2024, 42: lba8511-lba8511. DOI: 10.1200/jco.2024.42.17_suppl.lba8511.Peer-Reviewed Original ResearchTreatment-related adverse eventsDisease control ratePhase II studyEpidermal growth factor receptorKRAS G12C inhibitorsDose reduction/interruptionBrain metastasesII studySafety profileG12C inhibitorsBaseline PD-L1 expressionBaseline brain metastasesActivation of epidermal growth factor receptorPD-L1 expressionTreating NSCLC patientsAnti-EGFR antibodiesFront-line treatmentKRAS G12C mutationGrowth factor receptorNSCLC ptsNSCLC modelsTumor shrinkageFrontline therapyNSCLC patientsOpen-labelPreclinical development of ATR04-484, an auxotrophic strain of Staphylococcus epidermidis, for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity.
Whitfill T, Mootien S, Leger R. Preclinical development of ATR04-484, an auxotrophic strain of Staphylococcus epidermidis, for the topical treatment of epidermal growth factor receptor (EGFR) inhibitor-induced dermal toxicity. Journal Of Clinical Oncology 2024, 42: e24074-e24074. DOI: 10.1200/jco.2024.42.16_suppl.e24074.Peer-Reviewed Original ResearchEpidermal growth factor receptorMethicillin resistanceReconstructed human epidermisProphylactic settingS. aureusMRSA growthDermal toxicityColony-forming unitsPatients treated with EGFR inhibitorsTreatment of advanced lungTreatment of epidermal growth factor receptorSignaling pathwayStrains of Staphylococcus epidermidisEpidermal growth factor receptor pathwayQuality of lifeSuppress host defensesLevels of Staphylococcus aureusPig skinHuman cornea-like epitheliumS. aureus growthIrritation potentialCornea-like epitheliumAdherence to therapyInhibit S. aureusEGFR-mediated signaling pathwaysEGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Hu Z, Chen P, Li W, Krone M, Zheng S, Saarbach J, Velasco I, Hines J, Liu Y, Crews C. EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling. Science Advances 2024, 10: eadj7251. PMID: 38536914, PMCID: PMC10971414, DOI: 10.1126/sciadv.adj7251.Peer-Reviewed Original ResearchConceptsInhibit cancer cell viabilityProteome-wide levelCancer cell viabilityDifferential signaling pathwaysPhosphoproteomic approachTyrosine dephosphorylationProtein dephosphorylationSignal transductionActivating dephosphorylationInduce apoptosisReceptor tyrosine kinase inhibitorsRTK activationSignaling pathwayInhibition of kinasesDephosphorylationEpidermal growth factor receptorGrowth factor receptorCell viabilityFactor receptorInhibitory approachesTyrosineTyrosine kinase inhibitorsInhibitory effectInhibitory potentialKinase inhibitorsSummary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Tsuboi M, Herbst R, John T, Kato T, Majem M, Grohé C, Wang J, Goldman J, Lu S, de Marinis F, Shepherd F, Lee K, Le N, Dechaphunkul A, Kowalski D, Bonanno L, Dómine M, Poole L, Bolanos A, Rukazenkov Y, Wu Y. Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. Targeted Oncology 2024, 19: 131-134. PMID: 38466534, PMCID: PMC10963460, DOI: 10.1007/s11523-024-01034-3.Peer-Reviewed Original ResearchNon-small cell lung cancerEGFR-mutant non-small cell lung cancerResected EGFR-mutant non-small cell lung cancerEpidermal growth factor receptorOverall survivalEGFR-mutantStage IB-IIIA non-small cell lung cancerPatients treated with osimertinibDisease-free survivalStage II-IIIAEffects of osimertinibCell lung cancerGrowth factor receptorCancer cell deathRisk of deathADAURA studyLength of time patientsOsimertinib groupTumor shrinkagePlacebo groupCancer-freeOsimertinibLung cancerFactor receptorCancer cellsExecutive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer
Nagpal S, Milano M, Chiang V, Soltys S, Brackett A, Halasz L, Garg A, Sahgal A, Ahluwalia M, Tom M, Palmer J, Knisely J, Chao S, Gephart M, Wang T, Lo S, Chang E. Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer. Neuro-Oncology 2024, 26: 1195-1212. PMID: 38459978, PMCID: PMC11226873, DOI: 10.1093/neuonc/noae041.Peer-Reviewed Original ResearchNon-small cell lung cancerTyrosine kinase inhibitorsCell lung cancerCentral nervous systemAmerican Radium SocietyALK-fusionBrain metastasesAmerican Radium Society Appropriate Use CriteriaLung cancerSequence of tyrosine kinase inhibitorsALK tyrosine kinase inhibitorsTreatment of brain metastasesEGFR tyrosine kinase inhibitorsWhole-brain RTEpidermal growth factor receptorGrowth factor receptorAppropriate Use CriteriaBrain RTEGFR-mutantRadiotherapyTreatment optionsFactor receptorKinase inhibitorsNervous systemLiterature search
2023
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Desai J, Alonso G, Kim S, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller W, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim T, Moreno V, Ou S, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel M, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Jun T, Dharia N, Schutzman J, Han S. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nature Medicine 2023, 30: 271-278. PMID: 38052910, PMCID: PMC10803265, DOI: 10.1038/s41591-023-02696-8.Peer-Reviewed Original ResearchPhase 1b trialColorectal cancerSafety profileMedian progression-free survivalTreatment-related adverse eventsInhibitor-naive patientsKRAS G12C inhibitionAntitumor activityManageable safety profileObjective response rateProgression-free survivalPreliminary antitumor activityKRAS G12C mutationKRAS G12C inhibitorsEpidermal growth factor receptorVariant allele frequencyGrowth factor receptorAdverse eventsMedian durationTreatment withdrawalPoor prognosisDisease progressionArm CDose reductionG12C inhibitorsPatritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial
Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez R, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg D, Sellami D, Yonemori K. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3–Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3–Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. Journal Of Clinical Oncology 2023, 41: 5550-5560. PMID: 37801674, PMCID: PMC10730028, DOI: 10.1200/jco.23.00882.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsHuman epidermal growth factor receptor 3Epidermal growth factor receptor 3Metastatic breast cancerGrowth factor receptor 3Breast cancerReceptor 3Dose expansionPrevious therapyClinical subtypesCommon treatment-emergent adverse eventsPhase I/II trialHER2-positive breast cancerTriple-negative breast cancerDose-escalation partDose-expansion partManageable safety profileAdvanced breast cancerEpidermal growth factor receptorAntibody-drug conjugatesGrowth factor receptorAdvanced diseaseHematologic toxicityII trialObjective responseIncorporating clinicopathological and molecular risk prediction tools to improve outcomes in early HR+/HER2– breast cancer
Curigliano G, Dent R, Llombart-Cussac A, Pegram M, Pusztai L, Turner N, Viale G. Incorporating clinicopathological and molecular risk prediction tools to improve outcomes in early HR+/HER2– breast cancer. Npj Breast Cancer 2023, 9: 56. PMID: 37380659, PMCID: PMC10307886, DOI: 10.1038/s41523-023-00560-z.Peer-Reviewed Original ResearchOptimal treatment pathwayBreast cancerCyclin D kinase 4/6 inhibitorDifferent adjuvant treatment modalitiesFuture risk stratification strategiesSimilar prognostic accuracyAdjuvant treatment modalitiesEarly breast cancerRisk of recurrenceRisk stratification strategiesRisk prediction toolsIndividual patient levelEpidermal growth factor receptorBreast cancer diagnosisGrowth factor receptorTreatment guidelinesRisk stratificationMultigene assaysTreatment modalitiesClinical trialsPatient levelPrognostic accuracyTreatment pathwaysEarly breast cancer diagnosisLevel IOverall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Tsuboi M, Herbst R, John T, Kato T, Majem M, Grohé C, Wang J, Goldman J, Lu S, Su W, de Marinis F, Shepherd F, Lee K, Le N, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov Y, Wu Y. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. New England Journal Of Medicine 2023, 389: 137-147. PMID: 37272535, DOI: 10.1056/nejmoa2304594.Peer-Reviewed Original ResearchConceptsDisease-free survivalOverall survivalIIIA diseaseStage IBAdjuvant osimertinibPlacebo groupOsimertinib groupNew serious adverse eventsSignificant overall survival benefitStage IILonger disease-free survivalEnd pointData cutoff datePrevious adjuvant chemotherapyDouble-blind trialOverall survival benefitPrimary end pointSecondary end pointsSerious adverse eventsCell lung cancerCoronavirus disease 2019Epidermal growth factor receptorADAURA trialAdjuvant chemotherapyEligible patients
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