2025
KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects
Liu M, Townsend J. KRAS G12C-associated immunotherapy benefit in NSCLC is substantially mediated by tobacco-induced tumor mutation burden, not allele-specific effects. Lung Cancer 2025, 108749. DOI: 10.1016/j.lungcan.2025.108749.Peer-Reviewed Original ResearchNon-small cell lung cancerImmune-checkpoint inhibitionTumor mutational burdenMutational burdenG12C mutationLung adenocarcinomaElevated tumor mutation burdenHigh tumor mutational burdenOncogenic potentialCell lung cancerKRAS G12C mutationImmunotherapy benefitICI outcomesSmoking historyLung cancerG12D mutationHazard ratioAllele-specific effectsKRASClinical trendsKRAS G12CResponse rateTumorG12CMutations
2018
Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C
Cannataro VL, Gaffney SG, Stender C, Zhao ZM, Philips M, Greenstein AE, Townsend JP. Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C. Oncogene 2018, 37: 2444-2455. PMID: 29453361, DOI: 10.1038/s41388-017-0105-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SubstitutionAnimalsCase-Control StudiesDisease ProgressionDrug Resistance, NeoplasmFemaleGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansMaleMiceMice, Inbred BALB CMice, NudeNeoplasmsOncogenesPoint MutationPolymorphism, Single NucleotideProto-Oncogene Proteins p21(ras)Sequence Analysis, DNAYoung AdultConceptsTime of treatmentTargeted therapyLung tumorsDe novo mutationsNew targeted therapiesPatient-derived xenograftsHighest fitness advantageKRAS G12C variantNovo mutationsEvidence of heterogeneityNovel KRAS mutationPreclinical promiseSuch therapyHigh prevalenceKRAS mutationsTreatment resistanceBRAF V600EKRASTherapyTargeted inhibitorsTumorsAssociated oncogeneRAS genesHuman cancersOncogenic mutations
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