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Small-cell lung cancer, treated as one disease for fifty years, is at least four. The subtypes are named after the transcription factor each one leans on: ASCL1, NeuroD1, YAP1 and POU2F3.
Rudin, Poirier, Byers, Dive and eighteen colleagues proposed a working nomenclature for small-cell lung cancer subtypes defined by the relative expression of four key transcription regulators, ASCL1, NeuroD1, YAP1 and POU2F3, synthesising evidence from primary human tumours, patient-derived xenografts, cell lines and genetically engineered mouse models.
A consensus perspective rather than a study, and it is on this list because of what it enabled: once the subtypes had names, trials could be designed around them, and the therapeutic vulnerabilities that differ between them (DLL3 in ASCL1-high disease, PARP and checkpoint sensitivity elsewhere) became testable propositions rather than post hoc observations.
The organising framework for every small-cell lung cancer trial designed since. It is also why the slow progress in the disease is now attributed to treating four diseases as one rather than to the biology being intractable.
Small-cell lung cancer got its first targeted drug, and the mechanism is a T-cell engager rather than a kinase inhibitor. It also brought cytokine release syndrome, and the inpatient monitoring that goes with it, into thoracic oncology for the first time.
One of the most cited trial reports Europe PMC returns for DLL3 in Small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.
The case for re-biopsy at progression, for treating resistance as a diagnosis rather than an endpoint, and for the idea of a drug holiday. It is also the origin of resistance-directed sequencing: what you give next should depend on what the tumour became.
Shares Run small-cell lung cancer as one platform with shared controls and subtype stratification, Tarlatamab for patients with previously treated small-cell lung cancer, 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, Extensive-stage small-cell lung cancer and the tag lung-evidence.
Shares Histology, 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, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, 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, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares 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, Biomarkers are not validated or standardised, Rare and paediatric cancers without markets and the tag lung-evidence.
Shares Limited-stage small-cell lung cancer, 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, Biomarkers are not validated or standardised, Rare and paediatric cancers without markets and the tag lung-evidence.
Shares Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, 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), Small-cell lung cancer and the tag lung-evidence.
Shares Histology, 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, Biomarkers are not validated or standardised, Lung cancer (all types) and the tag lung-evidence.
Shares Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors, 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, Lung cancer (all types) and the tag lung-evidence.