Table 1. Different subtypes of SCLC, related genes/pathways, and corresponding treatment strategies.

Traditional classification of SCLCs	Characteristics	Related genes/pathways	Novel SCLC subtypes defined by transcriptional regulators	Major transcriptional factor	Related genes/pathways	Treatments
*, Therapeutic agents have only preliminary exploration results in SCLC subtypes or may become one of the treatments in the future; SCLC, small cell lung cancer; NE, neuroendocrine.
NE-high subtype	Classic SCLC morphology; Epithelial phenotype	ASCL1, INSM1, SYP, BEX1, CHGA, NKX2-1, DLL3, DLK1, HES6, TTF-1, CDH1	SCLC-A	ASCL1	MYCL, BCL2, SOX2, RET, NFIB, DLL3, DLK1, NKX2-1, INSM1, HES6, TTF-1	DLL3 inhibitors: Antibody-drug conjugate, rovalpituzumab teserine (Rova-T); Bispecific antibody T-cell technology (BiTE), AMG 757 (NCT03319940); Chimeric antigen receptor (CAR)-T, AMG119 (NCT03392064); BCL2 inhibitors: venetoclax; LSD1 inhibitors: (NCT02034123)
			SCLC-N	NEUROD1	MYC, MycT58A, INSM1, HES6	AURKA/B, CHK1, IMPDH1/2 inhibition; Arginine depletion; Oncolytic Seneca Valley virus (SVV); AURK inhibitors: Alisertib
NE-low subtype/non-NE SCLC	Variant form of SCLC; Mesenchymal phenotype	NOTCH, HES1, MYC, REST, ASCL2, HIPPO/ YAP1, TGF-β, EMT (vimentin, SNAI2, CD44), MYB, BCL2	SCLC-P	POU2F3	IFGR1 pathway, SOX9, ASCL2, MYC	Antimetabolites: anti-folates and nucleoside analogues; PARP inhibitors (veliparib, olaparib)
			SCLC-Y	YAP1	HIPPO signaling, intact RB1, overexpress MYC	mTOR inhibitors, PLK inhibitors*; CDK4/6 inhibitors*; YAP1 and NOTCH inhibitors*; ICIs*
					INF-γ gene, T-cell inflammatory GEP score, human leukocyte antigens (HLAs) gene, T-cell receptor gene, cGAS, STING
			SCLC-I/ inflamed	ASCL1−/NEUROD1−/POU2F3−	Inflamed: immune checkpoints, HLAs genes, STING, INF-γ pathway, T-cell inflammatory GEPs, immune cell infiltration	ICIs (atezolizumab); BTK inhibitor (imbruvica)*
					EMT: vimentin, AXL