# Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11

Source: https://onco.cc/terms/sclc-molecular-subtypes/  
OnCo record `sclc-molecular-subtypes` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: 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

## Connected records

- targets: [DLL3](https://onco.cc/targets/dll3/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Ifinatamab deruxtecan](https://onco.cc/drugs/ifinatamab-deruxtecan/), [Lurbinectedin](https://onco.cc/drugs/lurbinectedin/), [Tarlatamab](https://onco.cc/drugs/tarlatamab/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- cancers: [Extensive-stage small-cell lung cancer](https://onco.cc/cancers/extensive-stage-sclc/), [Limited-stage small-cell lung cancer](https://onco.cc/cancers/limited-stage-sclc/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)

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