2025
MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial
Gounder M, Johnson M, Heist R, Shapiro G, Postel-Vinay S, Wilson F, Garralda E, Wulf G, Almon C, Nabhan S, Aguado-Fraile E, He P, Romagnoli M, Hossain M, Narayanaswamy R, Sadou-Dubourgnoux A, Cooper M, Askoxylakis V, Burris H, Tabernero J. MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial. Nature Communications 2025, 16: 423. PMID: 39762248, PMCID: PMC11704051, DOI: 10.1038/s41467-024-55316-5.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesEvidence of clinical activityPaired tumor biopsiesTreatment-related toxicityPhase I trialPhase 1 trialFirst-in-humanLiver function testsProof-of-mechanismHomozygous MTAP deletionPlasma SAM concentrationsPartial responseConcentrations of S-adenosylmethionineTumor biopsiesI trialSafety profileMTAP deletionHomozygous deletionMAT2A inhibitionClinical activityPlasma concentrationsFunction testsPatientsSecondary objectivesMaximal reduction
2022
RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterations
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