Table 2.
SCLC molecular classification: nomenclature evolution along years and characteristics.
| Year | Neuroendocrine | Non-Neuroendocrine | ||
|---|---|---|---|---|
| 1985 [26] | Classic | Variant | ||
| 2013 [30] | ASCL1-high | NEUROD1-high | ||
| 2915 [21] | SC-E2 | SC-E1 | ||
| 2016 [31] | ASCL1-high | NEUROD1-high | Double negative | |
| 2017 [29] | INSM1 | YAP1 | ||
| 2018 [32] | POU2F3 | |||
| 2019 [27] | SCLC-A | SCLC-N | SCLC-P | SCLC-Y |
| 2021 [28] | SCLC-A | SCLC-N | SCLC-P | SCLC-I |
| Molecular subtype characteristics | ||||
| Proportion | 40–50% | 25–30% | 7–16% | 15% |
| Targets | MYCL1, BCL2, RET, SOX2, INSM1, NFIB, NOTCH, DLL3 | MYC, INSM1, HES6 | MYC, IGF1R | mTOR, PDL1, CDK4/6, IFNy |
| Potential targeted therapy | BCL2 inhibitors DLL3 inhibitors LSD1 inhibitors |
AURKA inhibitors PARP inhibitors |
IGFR1 inhibitors AURKA inhibitors PARP inhibitors |
ICIs mTOR inhibitors CDK4/6 inhibitors EMT reversal therapies |
ASCL1, achaete-scute homologue 1; NeuroD1, neurogenic differentiation factor 1; POU2F3, POU class 2 homeobox 3; YAP1, yes-associated protein 1; INSM1, insulinoma-associated protein 1; BCL2, B-cell lymphoma 2; DLL3, delta-like ligand 3; LSD1, lysine-specific histone demethylase 1; PARP, poly (ADP-ribose) polymerase; AURKA/B, Aurora kinase A/B; IGF-R1, insulin-like growth factor 1 receptor; ICIs, immuno checkpoint inhibitors; mTOR, mammalian target of rapamycin; CDK4/6, cyclin-dependent kinase 4/6; EMT, epithelial–mesenchymal transition.