2025
FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
Lubrano S, Cervantes-Villagrana R, Faraji F, Ramirez S, Sato K, Adame-Garcia S, Officer A, Arang N, Rigiracciolo D, Anguiano Quiroz P, Martini C, Wang Y, Ferguson F, Bacchiocchi A, Halaban R, Coma S, Holmen S, Pachter J, Aplin A, Gutkind J. FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma. Cancer Cell 2025, 43: 428-445.e6. PMID: 40020669, PMCID: PMC11903146, DOI: 10.1016/j.ccell.2025.02.001.Peer-Reviewed Original ResearchConceptsBRAF V600E melanomaFocal adhesion kinaseV600E melanomaFAK inhibitorActivated focal adhesion kinaseFocal adhesion kinase inhibitionRaf-MEKActivation of focal adhesion signalingFocal adhesion kinase inhibitorResistance to BRAFiSyngeneic mouse modelMAPK pathway inhibitionFocal adhesion signalingPro-apoptotic activityMelanoma patientsAdhesion signalingImmune therapyBRAF mutationsBRAFiTranscriptome analysisMelanomaMouse modelPathway inhibitionBRAFMelanoma cells
2024
1299P First-line immunotherapy versus BRAF and MEK inhibitors for patients with BRAF V600E mutant metastatic non-small cell lung cancer
Di Federico A, Chen M, Pagliaro A, Ogliari F, Stockhammer P, Aldea M, Grant M, De Giglio A, Alessi J, Pecci F, Gelsomino F, Negrao M, Ferrara R, Awad M, Riely G, Ardizzoni A, Planchard D, Offin M, Johnson B, Ricciuti B. 1299P First-line immunotherapy versus BRAF and MEK inhibitors for patients with BRAF V600E mutant metastatic non-small cell lung cancer. Annals Of Oncology 2024, 35: s826-s827. DOI: 10.1016/j.annonc.2024.08.1356.Peer-Reviewed Original ResearchOncogenic composite mutations can be predicted by co‐mutations and their chromosomal location
Küçükosmanoglu A, van der Borden C, de Boer L, Verhaak R, Noske D, Wurdinger T, Radonic T, Westerman B. Oncogenic composite mutations can be predicted by co‐mutations and their chromosomal location. Molecular Oncology 2024, 18: 2407-2422. PMID: 38757376, PMCID: PMC11459034, DOI: 10.1002/1878-0261.13636.Peer-Reviewed Original ResearchComposite mutationCo-mutationsMutation-specific drugsCell line dataChromosomal locationSub-clonal populationsGenetic heterogeneitySub-clonesTherapy resistanceSelection pressureGenetic eventsStratify patientsKRAS geneResistance-causing mutationsCancer patientsBiopsy samplesMutationsPatientsGenesPrecision medicineTherapyRiskChromosomeBiopsyBRAFBRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms
Gerami P, Chen A, Sharma N, Patel P, Hagstrom M, Kancherla P, Geraminejad T, Olivares S, Biswas A, Bosenberg M, Busam K, de La Fouchardière A, Duncan L, Elder D, Ko J, Landman G, Lazar A, Lowe L, Massi D, Mihic-Probst D, Parker D, Scolyer R, Shea C, Zembowicz A, Yun S, Blokx W, Barnhill R. BRAF Mutated and Morphologically Spitzoid Tumors, a Subgroup of Melanocytic Neoplasms Difficult to Distinguish From True Spitz Neoplasms. The American Journal Of Surgical Pathology 2024, 48: 538-545. PMID: 38525831, DOI: 10.1097/pas.0000000000002194.Peer-Reviewed Original Research
2023
The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer
Grant M, Woodard G, Goldberg S. The Evolving Role for Systemic Therapy in Resectable Non-small Cell Lung Cancer. Hematology/Oncology Clinics Of North America 2023, 37: 513-531. PMID: 37024389, DOI: 10.1016/j.hoc.2023.02.003.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerMetastatic non-small cell lung cancerResectable non-small cell lung cancerImmuno-oncology agentsHistologic classification systemUnited States FoodResectable tumorsSystemic therapyDriver alterationsDrug AdministrationStates FoodSystemic managementPatientsTherapyCancerEvolving roleClassification systemNTRKHER2TumorsKRASEGFRBRAFSpectrum and implications of activating BRAF alterations in advanced prostate cancer (aPC).
Chehrazi-Raffle A, Tukachinsky H, Schrock A, Hwang J, Zengin Z, Meza L, Chawla N, Ebrahimi H, Govindarajan A, Castro D, Rock A, Tripathi A, Dorff T, Pal S, Oxnard G, Agarwal N, Antonarakis E. Spectrum and implications of activating BRAF alterations in advanced prostate cancer (aPC). Journal Of Clinical Oncology 2023, 41: 220-220. DOI: 10.1200/jco.2023.41.6_suppl.220.Peer-Reviewed Original ResearchAdvanced prostate cancerComprehensive genomic profilingGenomic alterationsBRAF alterationsTissue biopsiesCancer typesFurther clinical investigationTMPRSS2-ERG fusionFoundationOne CDxMedian ageCommon genomic alterationsAPC patientsProstate cancerMolecular subtypesClinical investigationHigh incidenceActionable targetsBRAF rearrangementsCancer-related genesHotspot missense mutationsGenomic profilingBRAFCDK12 mutationsGenetic activationBiopsy
2021
TIL in Melanoma—Similar Approaches, Different Results, Unanswered Questions
Sznol M. TIL in Melanoma—Similar Approaches, Different Results, Unanswered Questions. Clinical Cancer Research 2021, 27: 5156-5157. PMID: 34413160, DOI: 10.1158/1078-0432.ccr-21-2450.Peer-Reviewed Original ResearchMutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600
2020
A smooth muscle‐derived, Braf‐driven mouse model of gastrointestinal stromal tumor (GIST): evidence for an alternative GIST cell‐of‐origin
Kondo J, Huh WJ, Franklin JL, Heinrich MC, Rubin BP, Coffey RJ. A smooth muscle‐derived, Braf‐driven mouse model of gastrointestinal stromal tumor (GIST): evidence for an alternative GIST cell‐of‐origin. The Journal Of Pathology 2020, 252: 441-450. PMID: 32944951, PMCID: PMC7802691, DOI: 10.1002/path.5552.Peer-Reviewed Original ResearchConceptsGastrointestinal stromal tumorsSmooth muscle cellsICC hyperplasiaMuscle cellsTyrosine kinase inhibitor imatinibFrequent driver eventsCommon mesenchymal tumorsSmooth muscle cell progenitorsDevelopment of GISTsKinase inhibitor imatinibLoss of Trp53ICC-DMPGut motilityStromal tumorsMesenchymal tumorsMouse modelInhibitor imatinibInterstitial cellsMutant BRAFBRAF expressionTumorsBRAFHyperplasiaCell progenitorsDriver events
2019
Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling
Khan SA, Ci B, Xie Y, Gerber DE, Beg MS, Sherman SI, Cabanillas ME, Busaidy NL, Burtness BA, Heilmann AM, Bailey M, Ross JS, Sher DJ, Ali SM. Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling. Head & Neck 2019, 41: 1928-1934. PMID: 30758123, PMCID: PMC6542589, DOI: 10.1002/hed.25634.Peer-Reviewed Original ResearchConceptsAnaplastic thyroid cancerComprehensive genomic profilingThyroid cancerGenomic alterationsGenomic profilingMedian patient ageAggressive thyroid cancerYears of agePotential therapeutic significanceUnique mutation patternsDifferent molecular pathwaysATC specimensPatient ageCommon genomic alterationsKRAS alterationsCancer-related genesBRAF V600ETherapeutic significanceCancerBRAFMolecular pathwaysPatientsMutation patternsNumber alterationsNRAS
2018
Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing
Kim AS, Bartley AN, Bridge JA, Kamel-Reid S, Lazar AJ, Lindeman NI, Long TA, Merker JD, J. AJ, Rimm DL, Rothberg PG, Vasalos P, Moncur JT. Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing. JAMA Oncology 2018, 4: 838-841. PMID: 29242895, PMCID: PMC6145687, DOI: 10.1001/jamaoncol.2017.4021.Peer-Reviewed Original ResearchConceptsLaboratory-developed testsPT responseCompanion diagnosticsClinical laboratory testingKRAS testingOncology CommitteeMAIN OUTCOMEUS FoodDrug AdministrationPractice characteristicsDiagnostic testingTumor contentProficiency testingVariant-specific differencesEGFRBRAFClinical diagnostic testingMajority of laboratoriesKRASAssaysLaboratory testingPerformance of laboratoriesKit manufacturersResponseParticipants
2017
Feasibility of monitoring advanced melanoma patients using cell‐free DNA from plasma
Gangadhar T, Savitch S, Yee S, Xu W, Huang A, Harmon S, Lieberman D, Soucier D, Fan R, Black T, Morrissette J, Salathia N, Waters J, Zhang S, Toung J, van Hummelen P, Fan J, Xu X, Amaravadi R, Schuchter L, Karakousis G, Hwang W, Carpenter E. Feasibility of monitoring advanced melanoma patients using cell‐free DNA from plasma. Pigment Cell & Melanoma Research 2017, 31: 73-81. PMID: 28786531, PMCID: PMC5742050, DOI: 10.1111/pcmr.12623.Peer-Reviewed Original ResearchConceptsCell-free DNAStage III/IV patientsTissue next-generation sequencingAdvanced melanoma patientsMonitoring of patientsPrevious therapyIV patientsAdvanced melanomaMelanoma patientsTumor burdenBlood drawUltra-deep sequencingPatientsPlasma mutationsLiquid biopsyNext-generation sequencingFrequent mutationsAllele fractionTherapyMore mutationsMutationsBiopsyMelanomaBRAFRole of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations—a meta-analysis
Vuong H, Altibi A, Duong U, Ngo H, Pham T, Tran H, Oishi N, Mochizuki K, Nakazawa T, Hassell L, Katoh R, Kondo T. Role of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations—a meta-analysis. Tumor Biology 2017, 39: 1010428317713913. PMID: 29037127, DOI: 10.1177/1010428317713913.Peer-Reviewed Original ResearchConceptsPapillary thyroid cancerTERT promoter mutationsDistant metastasisThyroid cancerPromoter mutationsRET/PTC rearrangementsBRAF mutationsPresence of distant metastasesAssessment of patient prognosisTumor risk stratificationAssociated with distant metastasisPapillary thyroid carcinomaMeta-analysisPredicting distant metastasisAssociation of BRAFRandom-effects modelThyroid carcinomaTERT promoterRisk stratificationPatient prognosisRas mutationsAdverse outcomesMetastasisIncreased riskBRAFPrognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma—A meta‐analysis
Vuong H, Altibi A, Duong U, Hassell L. Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma—A meta‐analysis. Clinical Endocrinology 2017, 87: 411-417. PMID: 28666074, DOI: 10.1111/cen.13413.Peer-Reviewed Original ResearchConceptsTERT promoter mutationsPapillary thyroid carcinomaPromoter mutationsRisk stratificationRisk stratification of papillary thyroid carcinomaAssociated with increased tumor aggressivenessManagement of papillary thyroid carcinomaGroup of papillary thyroid carcinomasPapillary thyroid carcinoma patientsPooled estimates of odds ratiosCombination of BRAFEstimates of odds ratiosRandom-effects modelCoexisting BRAFThyroid carcinomaPrognostic implicationsTumor aggressivenessClinicopathological implicationsBRAFClinical managementConcurrent BRAFRisk groupsOdds ratioVirtual Health LibraryWeb of ScienceTargeting BRAF-Mutant Colorectal Cancer: Progress in Combination Strategies
Sundar R, Hong D, Kopetz S, Yap T. Targeting BRAF-Mutant Colorectal Cancer: Progress in Combination Strategies. Cancer Discovery 2017, 7: 558-560. PMID: 28576843, PMCID: PMC5458523, DOI: 10.1158/2159-8290.cd-17-0087.Commentaries, Editorials and LettersKEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer
Krall E, Wang B, Munoz D, Ilic N, Raghavan S, Niederst M, Yu K, Ruddy D, Aguirre A, Kim J, Redig A, Gainor J, Williams J, Asara J, Doench J, Janne P, Shaw A, McDonald R, Engelman J, Stegmeier F, Schlabach M, Hahn W. KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer. ELife 2017, 6: e18970. PMID: 28145866, PMCID: PMC5305212, DOI: 10.7554/elife.18970.Peer-Reviewed Original ResearchConceptsALK inhibitionMAPK signalingResponse to BRAFLoss of Keap1Presence of multiple inhibitorsAltering cell metabolismLung cancer cellsResistant to inhibitionClinical responseDeletion screeningTargeted therapyRTK/Ras/MAPK pathwayNegative regulatorReactive oxygen speciesCell metabolismCancer cellsBRAFCancerous inhibitorMultiple inhibitorsEGFRKEAP1 lossPromote survivalKeap1/Nrf2 pathwayOxygen speciesALK
2014
Targeted agents: management of dermatologic toxicities.
Burtness B. Targeted agents: management of dermatologic toxicities. Journal Of The National Comprehensive Cancer Network 2014, 12: 793-6. PMID: 24853219, DOI: 10.6004/jnccn.2014.0192.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor inhibitorsGrowth factor receptor inhibitorsDermatologic side effectsQuality of lifeDermatologic toxicitiesCutaneous complicationsSkin complicationsTherapeutic mainstayReceptor inhibitorsCommon culpritsToxicity profileMTOR inhibitorsSide effectsCosmetic issuesAnticancer treatmentPotential infectionComplicationsTreatmentInhibitorsTherapyAgentsCancerInfectionMainstayBRAF
2013
Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers
Hu J, Stites E, Yu H, Germino E, Meharena H, Stork P, Kornev A, Taylor S, Shaw A. Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers. Cell 2013, 154: 1036-1046. PMID: 23993095, PMCID: PMC3844432, DOI: 10.1016/j.cell.2013.07.046.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAmino Acid MotifsAmino Acid SequenceAnimalsCell LineDimerizationEnzyme ActivationHumansMiceModels, MolecularMolecular Sequence DataMutationPhosphorylationProtein ConformationProtein KinasesProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-rafraf KinasesSequence AlignmentTryptophanConceptsN-terminal phosphorylationReceiver kinaseRaf kinaseActivation-loop phosphorylationPhosphorylation of CRAFConstitutively active mutantCis-autophosphorylationRaf activationActive mutantActivated CRAFActive kinaseMechanism of activationKinase activityActive conformationKinasePhosphorylationControl cellsRafCRAFDimerMutantsRasActivityMEKBRAF
2012
Driver Mutations in Melanoma: Lessons Learned From Bench-to-Bedside Studies
Mehnert JM, Kluger HM. Driver Mutations in Melanoma: Lessons Learned From Bench-to-Bedside Studies. Current Oncology Reports 2012, 14: 449-457. PMID: 22723080, PMCID: PMC4447200, DOI: 10.1007/s11912-012-0249-5.Peer-Reviewed Original ResearchConceptsDriver mutationsSpecific patient subsetsPotential therapeutic strategyPatient subsetsSomatic driver mutationsMetastatic melanomaBedside studiesUveal melanomaTherapeutic strategiesBRAFV600E mutationMalignant transformationMelanomaMolecular classificationDevelopment of inhibitorsHuman samplesMutationsMolecular biologyBRAFDisease
2011
Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring V600EBRAF
Xing F, Persaud Y, Pratilas C, Taylor B, Janakiraman M, She Q, Gallardo H, Liu C, Merghoub T, Hefter B, Dolgalev I, Viale A, Heguy A, De Stanchina E, Cobrinik D, Bollag G, Wolchok J, Houghton A, Solit D. Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring V600EBRAF. Oncogene 2011, 31: 446-457. PMID: 21725359, PMCID: PMC3267014, DOI: 10.1038/onc.2011.250.Peer-Reviewed Original ResearchConceptsHeterogeneity of clinical outcomesSpectrum of genetic alterationsLoss of p16INK4aDiversity of clinical phenotypesLoss of RB1Prevent tumor formationMEK-selective inhibitorsRB1 tumor suppressorV600EBRAF mutationRB1 alterationsMutant BRAFClinical benefitMitogen-activated protein kinase pathwayClinical outcomesBRAF signalingGenetic alterationsGenomic alterationsOncogenic BRAFClinical phenotypePTEN inactivationProtein kinase pathwayCritical oncogenesTumor formationBRAFHuman cancers
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