Living with small-cell lung cancer: This is orientation from public patient pages and guidelines, not advice for your case: your own team's instructions and 24-hour number come first. The timeline is the thing that catches people out. NICE NG122 (1.8.1) asks for an assessment by a thoracic oncologist within 1 week of deciding to recommend treatment, and (1.10.2) for radiotherapy to start during the first or second cycle of chemotherapy in limited-stage disease, so decisions arrive close together and the practical, financial and family arrangements are better made early than left. Written from NICE NG122 and the NHS, Roy Castle Lung Cancer Foundation, Macmillan, Cancer Research UK, Maggie's and Marie Curie patient pages, all read on 25 September 2026.
Molecular layer. One genotype and four states. Whole-genome sequencing of 110 tumours found biallelic inactivation of TP53 and RB1 in nearly all of them, sometimes through complex rearrangement rather than point mutation, so a mutation call reads lower (85.8% and 72.5% in the public deposit) than the biology; the two cases with intact RB1 reached the same end through chromothripsis and cyclin D1overexpression. NOTCH family inactivation in 25%, oncogenic TP73 rearrangements, and chromatin regulators (KMT2D 18.3%, EP300 10.8%, CREBBP 9.2%) make up most of the rest, with kinase mutations only in rare individual cases (George 2015).
Molecular layer. The heterogeneity is transcriptional. Four subtypes are defined by ASCL1, NEUROD1 and POU2F3 expression or by the absence of all three: in 174 patient samples, 69% were ASCL1-dominant, 17% NEUROD1-dominant, 7% POU2F3-positive and the rest double-negative, with 37% co-expressing ASCL1 and NEUROD1, far more overlap than laboratory models predicted (Rudin 2019, Baine 2020). Expression analysis resolved the fourth class as inflamed rather than YAP1-driven, and that class gained most from adding immunotherapy to chemotherapy; the others carry distinct vulnerabilities to PARP, Aurora kinase and BCL-2inhibition, and platinum shifts tumours towards the inflamed state, which would make subtype a moving target (Gay 2021).
Molecular layer. Subtype decides whether the surface target is there. ASCL1-dominant and NEUROD1-dominant tumours are neuroendocrine-marker high, TTF-1 high and DLL3 high; POU2F3 and other double-negative tumours are low for all three, so a DLL3-directed medicine addresses roughly the 86% that are neuroendocrine-high rather than the whole disease (Baine 2020).
Molecular layer. Some small-cell lung cancer starts as adenocarcinoma. Transformation under EGFRblockade requires RB1 and TP53 loss, which is present from the earliest adenocarcinoma stage and gives a 43-fold risk (Lee 2017, Offin 2019); after transformation the founder EGFR mutation is retained, platinum and etoposidework, checkpoint inhibitors produced no responses in 17 patients, and median survival is 10.9 months (Marcoux 2019).
Machine-readable versions
The same record for scripts and assistants; checked 2026-09-25. Data CC BY-NC 4.0, attribute “Data from OnCo (onco.cc)”.