{"entity":{"id":"sclc-molecular-subtypes","kind":"term","name":"Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11","aka":["SCLC-A","SCLC-N","SCLC-P","SCLC-I","ASCL1","NEUROD1","POU2F3","YAP1 subtype","inflamed SCLC","SCLC subtypes","small cell lung cancer molecular subtypes","SLFN11","SLFN11 expression","neuroendocrine-high","neuroendocrine-low","transcription factor subtype"],"tldr":"Small-cell lung cancer has looked like one disease for fifty years; RNA profiling now splits it by the master transcription factor in charge (ASCL1, NEUROD1, POU2F3, or none with an inflamed signature), and these groups, plus the DNA-damage protein SLFN11, are the first leads for matching drugs to a cancer that has had almost no biomarkers.","summary":"What is measured: the dominant transcription factor and an immune signature. How: RNA expression or immunohistochemistry for ASCL1, NEUROD1 and POU2F3 on the biopsy (the original YAP1 group was replaced by the inflamed SCLC-I group by Gay and colleagues in 2021), SLFN11 by immunohistochemistry, DLL3 expression (high in SCLC-A), MYC amplification (SCLC-N); ctDNA methylation classifiers are in development because biopsies are small. Roughly: SCLC-A about half, DLL3-high and BCL2-high; SCLC-N about a quarter, MYC-driven with AURKA dependence; SCLC-P about a tenth, tuft-cell-like, sensitive to PARP inhibitors and nucleoside analogues; SCLC-I about 15 percent, with longer survival on atezolizumab in an exploratory IMpower133 analysis. SLFN11 expression predicts platinum and PARP inhibitor sensitivity (SWOG S1929 talazoparib maintenance). What a result changes: nothing yet in standard care, where everyone receives platinum-etoposide with a PD-L1 inhibitor; the subtypes select trial arms (tarlatamab against DLL3 is not subtype-restricted, ifinatamab deruxtecan against B7-H3, lurbinectedin, AURKA and BCL2 inhibitors) and are used to study transformation from EGFR-mutant adenocarcinoma. Where it matters: small-cell lung cancer, limited and extensive stage.","asOf":"2026-09-17","links":[],"tags":[],"related":["dll3","tarlatamab","ifinatamab-deruxtecan","lurbinectedin","rna-seq","ihc","atezolizumab","durvalumab","parp"],"cancers":["sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/sclc-molecular-subtypes/","neighbours":{"target":[{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"ifinatamab-deruxtecan","kind":"drug","name":"Ifinatamab deruxtecan","route":"/drugs/ifinatamab-deruxtecan/"},{"id":"lurbinectedin","kind":"drug","name":"Lurbinectedin","route":"/drugs/lurbinectedin/"},{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"cancer":[{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","route":"/cancers/limited-stage-sclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}]}}