Research advances in targeting claudin 18.2 in pancreatic ductal adenocarcinoma treatment

Table 1 Summary of pancreatic cancer research involving analysis of claudin 18.2 expression

Experimental goal	Number/type of cases	Core results	Conclusions	Ref.
Study the expression of CLDN18.2 in normal pancreatic tissue, primary lesions, metastases, and intra-individual matched samples in patients with PDAC, NEN, and acinar cell carcinoma	24 cases of normal pancreatic tissue, 202 samples of primary lesions, 84 cases with metastasis, and 48 intra-individual matched samples	Positive rate: 59.2% in primary PDAC. 20% in NEN. 69.4% in lymph node metastasis. 65.7% in liver metastasis	In principle, many pancreatic cancer patients can benefit from CLDN18.2-based targeted therapy	Wöll et al[24]
Study on the expression of CLDN18.2 in PDAC paraffin specimens and prognosis in patients undergoing curative pancreatectomy	309 cases of PDAC treated with curative pancreatectomy	30.4% of patients had ≥ 75% of tumor cells with a staining intensity of ≥ 2+; median OS of patients with CLDN18.2 positivity (30 months) was significantly longer than that of patients with CLDN18.2 negativity (18 months)	In PDAC patients with lymph node metastasis and perineural invasion, CLDN18.2 expression can be used as a prognostic indicator	Lyu et al[25]
Study on the relationship between CLDN18.2 expression and EMT using PDAC tissue microarrays and whole sections	TMA cohort: 302 cases. Whole slide cohort: 84 cases. Precancerous lesion analysis: 10 cases with PanIN	The CLDN18.2 positivity rate correlated significantly with the degree of pathological differentiation of PDAC. None of the 6 vimentin-positive cases expressed CLDN18.2. All 10 cases of PanIN were CLDN18.2 positive, while the adjacent normal ductal epithelium was negative	Loss of CLDN18.2 expression is related to tumor invasion and metastasis. CLDN18.2 may be involved in early carcinogenic transformation and can be used as a marker for early diagnosis of PDAC or monitoring of precancerous lesions	Zhang et al[26]
Study on the correlation between CLDN18.2 expression and survival in patients with resectable PDAC	68 PDAC patients who underwent surgery	54.4% of cases were CLDN18.2 positive (30.8% with IHC staining intensity of 1+, 16.2% with 2+, and 7.4% with 3+)	CLDN18.2 can serve as a prognostic marker for PDAC	Kayikcioglu and Yüceer[27]

CLDN18.2: Claudin 18.2; PDAC: Pancreatic ductal adenocarcinoma; NEN: Neuroendocrine neoplasia; EMT: Epithelial-mesenchymal transition; TMA: Tissue microarray; PanIN: Pancreatic intraepithelial neoplasia; IHC: Immunohistochemistry; OS: Overall survival.

Table 2 Summary of research progress on claudin 18.2-targeting drugs in pancreatic cancer

Drug class	Drug name	Company	Indications	Clinical testing phase	Registration number
mAb	Zolbetuximab	Astellas Pharma/Baxter Oncology GmbH	CLDN18.2-positive metastatic pancreatic adenocarcinoma/pancreatic adenocarcinoma	2	CTR20220914
		Astellas Pharma Global Development, Inc.	Pancreatic adenocarcinoma metastatic/CLDN18.2-positive pancreatic adenocarcinoma	1	NCT06396091
	FG-M108	FutureGen Biopharmaceutical Co., Ltd.	Pancreatic cancer	3	NCT07383922/CTR20260995
	Osemitamab	Suzhou Transcenta Therapeutics Co., Ltd.	PDAC	2	NCT04495296
		Bristol Myers Squibb Co.	Pancreatic cancer	2	NCT04396821
	ASKB589	Jiangsu Aosaikang Biomedicine Co., Ltd.	Pancreatic cancer	2	CTR20202121
	AB-011	CARsgen Therapeutics Co., Ltd.	Pancreatic adenocarcinoma	1	NCT04400383
	FL-301	Flame Biosciences LLC	Pancreatic cancer	2	NCT05181865
ADC	CMG901 (AZD0901)	Astra Zeneca PLC	PDAC	2	NCT06219941
		Keymed Biomedical Technology (Chengdu) Co. Ltd.	Pancreatic cancer	1	NCT04805307
	ATG-022	Antengene (Hangzhou) Biologics Co. Ltd.	Pancreatic cancer	Preclinical	FDA
	BL-M05D1	Systimmune, Inc.	Advanced PDAC	1	NCT07021066
	SHR-A1904	Shanghai HengruiPharmaceutical Co., Ltd.	Advanced pancreatic adenocarcinoma	1	CTR20211290
	IBI343	InnoventBiologics (Suzhou) Co., Ltd.	PDAC	1	NCT5458219
			PDAC	1	NCT05458219
			Pancreatic cancer	3	NCT07066098
	E0-3021	CSPC Pharmaceutical Group Ltd./Elevation Oncology, Inc.	Pancreatic cancer	1	The details of the drug have not been disclosed
ADC	XNW27011	Evopoint Biosciences Co., Ltd.	Metastatic pancreatic adenocarcinoma	2	NCT06792435
	JS107	Shanghai Junshi Biosciences Co., Ltd.	Pancreatic cancer	1	CTR20223134/NCT05657418
	LM-302	LaNova Medicines (Zhejiang) Co., Ltd.	Pancreatic cancer	3	The details of the drug have not been disclosed
	SOT-102	SOTIO Biotech as	Advanced pancreatic adenocarcinoma/pancreatic adenocarcinoma	2	NCT05525286
		Excoso as	Pancreatic cancer	2	The details of the drug have not been disclosed
CAR-T	IMC-008	Suzhou Immunofoco Biotechnology Co., Ltd.	Pancreatic cancer	The details of the drug have not been disclosed	FDA
	SENL-215	Hebei Senlangbio Biotechnology Co., Ltd.	Pancreatic cancer	Preclinical	The details of the drug have not been disclosed
	DCTY-1502	Beijing Dingcheng Peptide Source Biotech Co., Ltd.	Pancreatic cancer	Preclinical	The details of the drug have not been disclosed
BsAb	SNG2002	Beijing Shenogen Pharma Group Ltd.	Pancreatic cancer	Preclinical	The details of the drug have not been disclosed
	QLS31905	Qilu Pharmaceutical Co., Ltd.	Pancreatic cancer	3	NCT07079228

mAb: Monoclonal antibodies; ADC: Antibody drug conjugates; BsAb: Bispecific antibodies; CAR-T: Chimeric antigen receptor T cell; CLDN18.2: Claudin 18.2; PDAC: Pancreatic ductal adenocarcinoma; FDA: United States Food and Drug Administration; CTR: Clinical trial registration; NCT: National clinical trial.