TABLE 1.

Lung cancer research utilizing lung organoid models.

Organoids	Cell types	Features	Mechanism	Drug testing	References
LCOs	Adenocarcinoma	Derived from primary lung cancer tissues and paired non-neoplastic airway tissues	—	Olaparib	Kim et al. (2019)
	SCC	Own a greater long-term expansion potential		Erlotinib
	ASC	Maintain histological and genetic characteristics		Crizotinib
	LCNEC
	SCLC
LCOs	Cells derived from SCLC patients	A amicrophysiological system	—	Cisplatin	Jung et al. (2019)
		Enabled LCO culturing		Etoposide
		Finished drug sensitivity tests
AOs	NSCLC	Human airway organoids from broncho-alveolar	The dramatic causes of RSV infection and the neutrophil–epithelium interaction in epithelial airway organoids	Paclitaxel	Sachs et al. (2019)
	CF cell	Modeled RSV infections		Methotrexate
		Presented the direct effects of the viral protein NS2		Crizotinib cisplatin
LUAD organoids	PC-9 cancer cell	High cultivation success rate	Examined the effect of podoplanin (+) CAFs on the proliferation of cancer cells in the hybrid cancer organoids	—	Nakamura et al. (2019)
	CAFs	Co-cultured the generation of hybrid cancer organoids
		Contains both cancer cells and podoplanin (+) CAFs
LUAD and LUSC organoids	ASC	Cultured short-term and long-term organoids	—	Trametinib	Shi et al. (2020)
		Preserve the mutation and copy number landscape		Selumetinib
		Combination therapy in NSCLC organoids		BGJ398+
				Trametinib
				Combination
LCOs	NCI-H460	Cultured the cisplatin-resistant lung cancer organoids	HF induced G0/G1 phase arrest and apoptosis	HF, cisplatin	Li et al. (2021)
	NCI-H1299	Evaluated the combination of cisplatin and HF	HF affected PI3K/AKT and MAPK signaling pathways
AT2 organoid	AT2 cell prominent cell of origin for LUAD	Organoid models of KRAS, BRAF, and ALK mutant	Chromosomal inversion leads to an oncogenic fusion between Eml4 and Alk using CRISPR/Cas9 technologies	—	Naranjo et al. (2022)
		Cultured cell lines in F7 NHCS and growth factor-depleted media
		Tracked tumor-immune interactions in transplanted antigen-expressing organoids
LCOs	Adenocarcinoma	Provided a personalized platform for the treatment of patients with unknown lung cancer	Osimertinib, BLU-667, and the combination of three groups showed great differences in proteomic profiles which indicated the mechanisms of drug resistance	Osimertinib	Wang et al. (2023)
	SCC	Tested both targeted therapy and chemotherapy		Nabpaclitaxel
	SCLC			Pemetrexed
	ASC pulmonary sarcomatous carcinoma			Carboplatin etoposide cisplatin
PDOs	PDCC isolated from the malignant pleural effusion	Provided a model system that enables intimate investigation of the behaviors of cancer cells in the body	PDSs contributed to the enhancement of TGF-β to induce EMT, while PDOs attenuated it	—	Surina et al. (2023)
		Compared the PDSs and PDO in both the interaction to the immune systems and to the stroma
LCOs	LUAD	Used genetic engineering to make the induction of Wnt independency by EGFR/Ras alterations	Wnt-dependent and –independent phenotypes in lung adenocarcinoma are defined by NKX2-1 expression	Porcupine inhibitor (C59)	Ebisudani et al. (2023)
	LUSC	Introduced sgRNA targeting NKX2-1 into three lines of NKX2-1+ WRi LUAD organoids	Loss of the NKX2-1 sensitizes human lung adenocarcinomas to Wnt-targeting therapy
	SCLC	Used targeting Wnt signaling for the treatment of LUAD
	LCNEC

NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; SCC, squamous cell carcinoma; ASCs, adenosquamous carcinoma cells; LCNEC, large cell neuroendocrine carcinoma; LCO, lung cancer organoid; AOs, airway organoids; RSV, respiratory syncytial virus; CF, cystic fibrosis; LUAD, lung adenocarcinoma; CAFs, cancer-associated fibroblasts; LUSC, lung squamous cell carcinoma; HF, halofuginone; AT2, alveolar type 2; PDOs, patient-derived oganoids.