Clinical relevance of stem cells in lung cancer

Table 1 Potential therapeutic strategies targeting lung cancer stem cell markers

Stem cell marker-target	Therapeutic strategies in clinical trials and preclinical studies
Differentiation cluster
CD133	Docetaxel-loaded liposomes conjugated to anti-CD133 aptamers
	Gefitinib-loaded nanomicelles conjugated to anti-CD133 aptamers
	Salinomycin sodium-loaded nanoparticles conjugated to anti-CD133 antibody
	CD133-specific CAR-T cells plus anti-PD-1 antibody and a CD73 inhibitor
CD44	Salazosulfapyridine plus cisplatin and pemetrexed (Phase I clinical trial for the treatment of advanced non-squamous NSCLC)
	mAb MEM-85 (monoclonal antibody)
	HA-Cisplatin conjugated
	HA-Irinotecan conjugated (Phase II study for treatment of SCLC)
	HA-Apoferritin conjugated
	HA-conjugated cisplatin-loaded nanoparticles
Cell adhesion molecules
EpCAM	Doxorubicin-loaded nanoparticles conjugated to EpCAM aptamer
	Catumaxomab BsAb anti-human EpCAM/CD3 T-cell antigen (Phase I study for treatment of NSCLC)
	MT110 BsAb anti-EpCAM/CD3 T-cell antigen (Phase I clinical trial for treatment of lung adenocarcinoma)
	MuS110 BsAb anti-human EpCAM/CD3 T-cell antigen
	2C11x4-7 BsAb anti-murine EpCAM/CD3 T-cell antigen
Cell membrane transporters
ABCG2	Secalonic acid D
	Axitinib in combination with topotecan or mitoxantrone
	FL118 (topoisomerase 1 inhibitor) in combination with irinotecan, topotecan or cisplatino
	A-803467 (tetrodotoxin-resistant sodium channel blocker) in combination with topotecan, doxorubicin or mitoxantrone
	Verteporfin (YAP1 inhibitor)
Metabolic enzymes
ALDH	Disulfiram in combination with cisplatin plus vinorelbine (Phase II clinical trial for the treatment of NSCLC)
	Disulfiram alone or in combination with diethylaminobenzaldehyde and cisplatin
	FL118 in combination withirinotecan, topotecan or cisplatino
Transcription factors and signaling pathway
Oct-4	FL118 in combination with irinotecan, topotecan or cisplatino
Notch-signaling pathway	BsAb-5 directed against c-MET and CTLA-4 in CD166+ NSCLC

mAb: Monoclonal antibody; HA: Hyaluronic acid; BsAb: Bispecific antibody; CAR-T: Chimeric antigen receptor T; c-MET: Cellular mesenchymal-to-epithelial transition factor; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; NSCLC: Non-small cell lung cancer; ABCG2: ATP-binding cassette subfamily G member 2; CD133: Cluster of differentiation-133; CD44: Cluster of differentiation-44; EpCAM: Epithelial cell adhesion molecule; ALDH: Aldehyde dehydrogenase; Oct-4: Octamer-binding transcription factor 4.