CDH17 (Cadherin 17)

Natural compounds (neferine, ajoene, baicalein, isoliensinine, curcumin analogs) and synthetic drugs (5-FU, oxaliplatin, irinotecan, norcantharidin, cordycepin) modulate EMT and trigger ferroptosis, cuproptosis, paraptosis, and autophagy...Simultaneous targeting of EMT, CR-CSC maintenance, and chemoresistance using multifunctional natural and synthetic agents represents a promising strategy in CRC therapy. Induction of alternative cell death pathways may improve response, minimize relapse, and enable combinatorial regimens for resistant tumors.

CDH17 silencing reversed DDP resistance in GC cells, primarily through inhibition of the Warburg effect mediated by the Wnt/β-catenin signaling pathway.

Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs.

In vivo, CDH17 suppression resulted in 80-95% tumour growth suppression (Mean Difference (MD) = -96.67, 95% CI: &lsqb;-144.35, -48.98], p < 0.0001), with immunohistochemistry confirming cytoplasmic β-catenin sequestration and lower cyclin D1 levels. Collectively, these findings show CDH17 as a critical upstream effector sustaining Wnt/β-catenin signalling, cancer progression, tumour proliferation, stem cell properties, and metastasis, and support CDH17 inhibition as a promising therapeutic target across multiple cancer types.

Furthermore, CEACAM5, KLK1, and CD14 correspond to existing drugs. These proteins may deepen our comprehension of the etiology and could serve as appealing novel biomarkers and drug targets for NSCLC management.

P1, N=68, Recruiting, Arbele Pty Ltd | Trial completion date: Aug 2025 --> May 2026 | Trial primary completion date: Nov 2024 --> Mar 2026

CDH17 expression was evident in the LS174T tumor capsule tissue. In this study, we developed three nanobody-based tracers targeting CDH17, of which &lsqb;68Ga]Ga-NOTA-CDH1 and &lsqb;18F]AlF-RESCA-CDH1 noninvasively demonstrated CDH17 expression in preclinical models.

These findings suggest that CDH17 may have a dual role-maintaining adhesion in low-grade tumors while facilitating tumor emboli-related dissemination. CDH17 expression, particularly in the tumor emboli, could serve as a valuable prognostic biomarker in CRC with LVI.

Moreover, the BsADC displayed an advantageous safety profile in mice. These findings suggest that the CDH17-GUCY2C BsADC, which induces ferroptosis in tumor cells, could be a promising new treatment for colorectal cancer.

CGI hypermethylation and non-CGI hypomethylation are tightly linked and may co-emerge during the early stages of gastric carcinogenesis. Their concurrent presence in non-cancerous mucosa from PEGC patients suggests a coordinated epigenetic landscape contributing to residual cancer risk after H. pylori eradication.

Meanwhile, we found that KLF9 could restrain the transcription and expression of cadherin-17 (CDH17), suppressing the malignant progression and metastasis of NPC. This research expands our comprehension of transcription factor expression regulation from the perspective of protein acetylation and ubiquitination interactions, providing novel molecular markers and therapeutic targets for NPC.

Mir-200c inhibits pancreatic cancer cell proliferation and migration through dual mechanisms: activation of PTPN6 transcription and repression of CDH17 expression. These findings suggest that mir-200c, particularly when delivered via LNP systems, may serve as a promising therapeutic strategy for pancreatic cancer.