Loading
The Sherlock-Lung study sequenced 232 lung cancers from people who never smoked and found three distinct types, none of them carrying the tobacco damage signature. One type appears to begin decades before it is diagnosed.
Zhang, Joubert, Ansari-Pour and colleagues, with Landi as senior author, performed high-coverage whole-genome sequencing of 232 lung cancers in never smokers and defined three subtypes by copy-number aberration, named piano, mezzo-forte and forte.
The dominant piano subtype is rare in smokers' lung cancer: low mutational burden, high intratumour heterogeneity, long telomeres, frequent KRAS mutations, stem cell-like properties and slow growth, with driver progenitor cells datable to many years before diagnosis. Mezzo-forte carries specific amplifications and EGFR mutations; forte is defined by whole-genome doubling. No strong tobacco smoking signatures were detected, even in cases with secondhand smoke exposure.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
Shares Tracking the evolution of non-small-cell lung cancer, Clonal evolution & minimal residual disease, Tumour heterogeneity and clonal evolution, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch and the tag lung-evidence.
Shares Tracking the evolution of non-small-cell lung cancer, Clonal evolution & minimal residual disease, Tumour heterogeneity and clonal evolution, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.
Shares Tracking the evolution of non-small-cell lung cancer, Tumour heterogeneity and clonal evolution, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Lung cancer (all types) and the tag lung-evidence.
Shares Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, The hardest cancers are found late, National Cancer Institute (NIH), Lung cancer (all types) and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.