ArticleCell death discovery2024
Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Discovery of novel coumarin-containing triazolo[1,5-a]pyrimidine derivatives as potent ABCB1 inhibitor for modulation of multidrug resistance.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- Targeting angiopoietin-like protein 3 and interleukin-1β alleviated liver and kidney injury through attenuation of lipotoxicity and regulation of glycolipid metabolism in db/db mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Autophagy initiation inhibition combined with chemotherapy reverses drug resistance in oral cancer.Discover oncology · 2026Review
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
- Advances of Peptide-Drug Conjugates in the Treatment of Digestive System Tumors.Drug design, development and therapy · 2026Review
- Gastrointestinal cancer: molecular pathogenesis and targeted therapy.Molecular biomedicine · 2025Review
- Article
- Review
- Deciphering the dual role of autophagy in gastric cancer and gastroesophageal junction cancer: from tumor suppression to cancer progression.Discover oncology · 2025Review
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- A novel and promising therapeutic approach for treating pancreatic cancer: Nectin‑4‑targeted antibody‑drug conjugates alone or combined with autophagy inhibitors.International journal of molecular medicine · 2025Article
- Expression of Claudin18.2 in metastatic lesions in peritoneum of gastric cancer.Journal of gastrointestinal oncology · 2025Article
- Eco-friendly pomegranate production: Balancing energy consumption and environmental impact.PloS one · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Claudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, the inconclusive underlying mechanisms pose a hurdle to extending the utility of these agents. In our study, αCLDN18.2-MMAE, an ADC composed of an anti-CLDN18.2 monoclonal antibody and the tubulin inhibitor MMAE, induced a dose-dependent apoptosis via the cleavage of caspase-9/PARP proteins in CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy was remarkably activated during the αCLDN18.2-MMAE treatment, which was characterized by the accumulation of autophagosomes, the conversion of autophagy marker LC3 from its form I to II, and the complete autophagic flux. Inhibiting autophagy by autophagy inhibitor LY294002 remarkably enhanced αCLDN18.2-MMAE-induced cytotoxicity and caspase-mediated apoptosis, indicating the cytoprotective role of autophagy in CLDN18.2-directed ADC-treated gastric cancer cells. Combination with an autophagy inhibitor significantly potentiated the in vivo antitumoral efficacy of αCLDN18.2-MMAE. Besides, the Akt/mTOR pathway inactivation was demonstrated to be implicated in the autophagy initiation in αCLDN18.2-MMAE-treated gastric cancer cells. In conclusion, our study highlighted a groundbreaking investigation into the mechanism of the CLDN18.2-directed ADC, focusing on the crucial role of autophagy, providing a novel insight to treat gastric cancer by the combination of CLDN18.2-directed ADC and autophagy inhibitor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.