2023
Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA
Abbosh C, Frankell A, Harrison T, Kisistok J, Garnett A, Johnson L, Veeriah S, Moreau M, Chesh A, Chaunzwa T, Weiss J, Schroeder M, Ward S, Grigoriadis K, Shahpurwalla A, Litchfield K, Puttick C, Biswas D, Karasaki T, Black J, Martínez-Ruiz C, Bakir M, Pich O, Watkins T, Lim E, Huebner A, Moore D, Godin-Heymann N, L’Hernault A, Bye H, Odell A, Roberts P, Gomes F, Patel A, Manzano E, Hiley C, Carey N, Riley J, Cook D, Hodgson D, Stetson D, Barrett J, Kortlever R, Evan G, Hackshaw A, Daber R, Shaw J, Aerts H, Licon A, Stahl J, Jamal-Hanjani M, Birkbak N, McGranahan N, Swanton C. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA. Nature 2023, 616: 553-562. PMID: 37055640, PMCID: PMC7614605, DOI: 10.1038/s41586-023-05776-4.Peer-Reviewed Original ResearchConceptsCirculating tumor DNANon-small-cell lung cancerMetastatic disseminationClinical outcomesPlasma samplesEarly-stage non-small-cell lung cancerCirculating tumor DNA levelsCirculating tumor DNA detectionCytotoxic adjuvant therapyPreoperative ctDNA detectionResidual tumor cellsLongitudinal plasma samplesCancer cell fractionBiomarker of relapseProcess of metastatic disseminationAnalysis of plasma samplesClinical relapseDisease relapseAdjuvant therapyTumor DNAPreoperative plasmaRadiological surveillanceCtDNA detectionPatient cohortTumor cellsThe evolution of lung cancer and impact of subclonal selection in TRACERx
Frankell A, Dietzen M, Al Bakir M, Lim E, Karasaki T, Ward S, Veeriah S, Colliver E, Huebner A, Bunkum A, Hill M, Grigoriadis K, Moore D, Black J, Liu W, Thol K, Pich O, Watkins T, Naceur-Lombardelli C, Cook D, Salgado R, Wilson G, Bailey C, Angelova M, Bentham R, Martínez-Ruiz C, Abbosh C, Nicholson A, Le Quesne J, Biswas D, Rosenthal R, Puttick C, Hessey S, Lee C, Prymas P, Toncheva A, Smith J, Xing W, Nicod J, Price G, Kerr K, Naidu B, Middleton G, Blyth K, Fennell D, Forster M, Lee S, Falzon M, Hewish M, Shackcloth M, Lim E, Benafif S, Russell P, Boleti E, Krebs M, Lester J, Papadatos-Pastos D, Ahmad T, Thakrar R, Lawrence D, Navani N, Janes S, Dive C, Blackhall F, Summers Y, Cave J, Marafioti T, Herrero J, Quezada S, Peggs K, Schwarz R, Van Loo P, Miedema D, Birkbak N, Hiley C, Hackshaw A, Zaccaria S, Jamal-Hanjani M, McGranahan N, Swanton C. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature 2023, 616: 525-533. PMID: 37046096, PMCID: PMC10115649, DOI: 10.1038/s41586-023-05783-5.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerDisease-free survivalCell lung cancerWhole-genome doublingLung cancerLung adenocarcinomaAssociated with shorter disease-free survivalShorter disease-free survivalEvolution of lung cancerPattern of relapseSubclonal selectionPrimary study endpointHistory of smokingSubclonal expansionsCopy number instabilityEGFR mutationsCancer-associated mortalityCopy number heterogeneityClinical outcomesStudy endpointIntratumour heterogeneityNever-smokersClonal expansionFollow-upOncogenic isoform
2022
RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma
East P, Kelly G, Biswas D, Marani M, Hancock D, Creasy T, Sachsenmeier K, Swanton C, Downward J, de Carné Trécesson S. RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma. Nature Communications 2022, 13: 5632. PMID: 36163168, PMCID: PMC9512813, DOI: 10.1038/s41467-022-33290-0.Peer-Reviewed Original ResearchConceptsResponse to chemotherapyLung adenocarcinomaRas oncogene activationOncogenic activityKRAS wild-type tumorsReduced response to chemotherapyWild-type tumorsKRAS mutant tumorsResistance to therapyCohort of patientsAdverse clinical outcomesResponse to treatmentRAS pathway activationActive patient groupAggressive diseaseMutant tumorsKRAS mutationsClinical outcomesPreclinical studiesActivating mutationsClinical decision-makingGenetic alterationsPatient stratificationPatient groupKRAS
2021
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition
Litchfield K, Reading J, Puttick C, Thakkar K, Abbosh C, Bentham R, Watkins T, Rosenthal R, Biswas D, Rowan A, Lim E, Al Bakir M, Turati V, Guerra-Assunção J, Conde L, Furness A, Saini S, Hadrup S, Herrero J, Lee S, Van Loo P, Enver T, Larkin J, Hellmann M, Turajlic S, Quezada S, McGranahan N, Swanton C. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021, 184: 596-614.e14. PMID: 33508232, PMCID: PMC7933824, DOI: 10.1016/j.cell.2021.01.002.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCD8 AntigensChemokine CXCL13Chromosomes, Human, Pair 9Cohort StudiesCyclin D1DNA Copy Number VariationsExomeGene AmplificationHumansImmune Checkpoint InhibitorsImmune EvasionMultivariate AnalysisMutationNeoplasmsPolymorphism, Single NucleotideReceptors, CCR5T-LymphocytesTumor BurdenConceptsTumor mutational burdenTumor-infiltrating lymphocytesHistocompatibility leukocyte antigenCheckpoint inhibitorsCD8 tumor-infiltrating lymphocytesCPI-treated patientsTumor cell-intrinsicClinical outcome criteriaCopy-number analysisCXCL9 expressionCCND1 amplificationMutational burdenLeukocyte antigenTumor typesMultivariate predictorsSingle-cell RNA sequencingAdaptive immunityAssociated with resistanceWhole exomeMicroenvironmental featuresOutcome criteriaCopy-numberFunctional evidenceRNA-seqTumor
2020
The T cell differentiation landscape is shaped by tumour mutations in lung cancer
Ghorani E, Reading J, Henry J, Massy M, Rosenthal R, Turati V, Joshi K, Furness A, Ben Aissa A, Saini S, Ramskov S, Georgiou A, Sunderland M, Wong Y, Mucha M, Day W, Galvez-Cancino F, Becker P, Uddin I, Oakes T, Ismail M, Ronel T, Woolston A, Jamal-Hanjani M, Veeriah S, Birkbak N, Wilson G, Litchfield K, Conde L, Guerra-Assunção J, Blighe K, Biswas D, Salgado R, Lund T, Bakir M, Moore D, Hiley C, Loi S, Sun Y, Yuan Y, AbdulJabbar K, Turajilic S, Herrero J, Enver T, Hadrup S, Hackshaw A, Peggs K, McGranahan N, Chain B, Swanton C, Quezada S. The T cell differentiation landscape is shaped by tumour mutations in lung cancer. Nature Cancer 2020, 1: 546-561. PMID: 32803172, PMCID: PMC7115931, DOI: 10.1038/s43018-020-0066-y.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor mutational burdenT cellsUntreated non-small cell lung cancerLung cancerCD8 T cell differentiationHigh-dimensional flow cytometryAssociated with poor survivalPersistent antigen exposureCD8 T cellsCD4 T cellsCell lung cancerT cell functionT cell differentiationImmunotherapy outcomesTumor neoantigensUntreated tumorsMutational burdenAntigen exposureTumor mutationsPoor survivalCancer cohortGene signatureTherapeutic manipulationFlow cytometry