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 cells
2020
Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors
Li J, Duran M, Dhanota N, Chatila W, Bettigole S, Kwon J, Sriram R, Humphries M, Salto-Tellez M, James J, Hanna M, Melms J, Vallabhaneni S, Litchfield K, Usaite I, Biswas D, Bareja R, Li H, Martin M, Dorsaint P, Cavallo J, Li P, Pauli C, Gottesdiener L, DiPardo B, Hollmann T, Merghoub T, Wen H, Reis-Filho J, Riaz N, Su S, Kalbasi A, Vasan N, Powell S, Wolchok J, Elemento O, Swanton C, Shoushtari A, Parkes E, Izar B, Bakhoum S. Metastasis and Immune Evasion from Extracellular cGAMP HydrolysisENPP1, a Therapeutic Target in Chromosomally Unstable Tumors. Cancer Discovery 2020, 11: 1212-1227. PMID: 33372007, PMCID: PMC8102348, DOI: 10.1158/2159-8290.cd-20-0387.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHumansHydrolysisImmunotherapyMiceMice, Inbred BALB CNeoplasm MetastasisNeoplasmsNucleotides, CyclicTumor EscapeConceptsChromosomally unstable tumorsAnti-PD-1/PD-L1 treatmentResponse to immune checkpoint blockadeReduced immune cell infiltrationUnstable tumorsGeneration of extracellular adenosineCancer cells to immune cellsImmune-suppressive pathwaysImmune checkpoint blockadeResistance to immunotherapyTumor immune infiltrationImmune cell infiltrationEvading immune surveillanceMetastatic cancer cellsCGAS-STING innate immune pathwayExtracellular cGAMPCheckpoint blockadeInnate immune pathwaysTumor inflammationImmune surveillanceExtracellular adenosineImmune infiltrationIncreased metastasisImmune cellsCell infiltrationPervasive chromosomal instability and karyotype order in tumour evolution
Watkins T, Lim E, Petkovic M, Elizalde S, Birkbak N, Wilson G, Moore D, Grönroos E, Rowan A, Dewhurst S, Demeulemeester J, Dentro S, Horswell S, Au L, Haase K, Escudero M, Rosenthal R, Bakir M, Xu H, Litchfield K, Lu W, Mourikis T, Dietzen M, Spain L, Cresswell G, Biswas D, Lamy P, Nordentoft I, Harbst K, Castro-Giner F, Yates L, Caramia F, Jaulin F, Vicier C, Tomlinson I, Brastianos P, Cho R, Bastian B, Dyrskjøt L, Jönsson G, Savas P, Loi S, Campbell P, Andre F, Luscombe N, Steeghs N, Tjan-Heijnen V, Szallasi Z, Turajlic S, Jamal-Hanjani M, Van Loo P, Bakhoum S, Schwarz R, McGranahan N, Swanton C. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature 2020, 587: 126-132. PMID: 32879494, PMCID: PMC7611706, DOI: 10.1038/s41586-020-2698-6.Peer-Reviewed Original ResearchConceptsSomatic copy number alterationsWhole-genome doublingChromosomal instabilityHuman leukocyte antigenChromosomal instability resultsSomatic copy number alteration analysisLoss of chromosome 8pFocal somatic copy number alterationsLoss of heterozygosityCopy number alterationsMetastatic samplesTumor evolutionKaryotype remodelingChromosome 8q24.1Clear cell renal cellChromosome 1q21Evolutionary eventsHER2+ breast cancerChromosome 8pChromosome 11q13.3Focal amplificationHaploid copiesRecurrent lossSubclonal frequenciesClonal events
2019
Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse
Chemi F, Rothwell D, McGranahan N, Gulati S, Abbosh C, Pearce S, Zhou C, Wilson G, Jamal-Hanjani M, Birkbak N, Pierce J, Kim C, Ferdous S, Burt D, Slane-Tan D, Gomes F, Moore D, Shah R, Al Bakir M, Hiley C, Veeriah S, Summers Y, Crosbie P, Ward S, Mesquita B, Dynowski M, Biswas D, Tugwood J, Blackhall F, Miller C, Hackshaw A, Brady G, Swanton C, Dive C. Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse. Nature Medicine 2019, 25: 1534-1539. PMID: 31591595, PMCID: PMC6986897, DOI: 10.1038/s41591-019-0593-1.Peer-Reviewed Original ResearchConceptsNon-small-cell lung cancerEarly-stage non-small-cell lung cancerDisease relapseGenomic profilingHigh risk of recurrenceDetection of circulating tumor cellsRisk of recurrenceTumor cell disseminationTime of surgeryPredictors of relapsePotential clinical utilityCurative intentPrimary tumorSurgical resectionTumor resectionTumor stagePredicting relapseCell disseminationTumor cellsLung cancerMutational overlapRelapseMultivariate analysisSurgeryHigh risk