ArticleBritish journal of cancer2018
Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Novel syngeneic model of anti-mouse CLDN18.2 CAR -T therapy for gastric cancer demonstrates a synergy with TGF-β and PD-L1 inhibitors.Molecular therapy. Oncology · 2026Article
- Differentially expressed microRNA in prognosis of gastric cancer with Lauren classification.Cancer biomarkers : section A of Disease markers · 2024Article
- Artificial intelligence-guided discovery of gastric cancer continuum.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Genetic and Epigenetic Alterations ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications.Frontiers in molecular biosciences · 2021Review
- The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies.Open biology · 2020Review
- Establishment of TP53-knockout canine cells using optimized CRIPSR/Cas9 vector system for canine cancer research.BMC biotechnology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiffuse-type gastric cancer (DGC) exhibits rapid disease progression and poor patient prognosis. We have previously established an E-cadherin/p53 double conditional knockout (DCKO) mouse line as the first genetically engineered one, which morphologically and molecularly recapitulates human DGC. In this study, we explored low-molecular-weight drugs selectively eliminating mouse and human DGC cells.
methodsWe derived mouse gastric cancer (GC) cell lines from DGC of the DCKO mice demonstrating enhanced tumourigenic activity in immunodeficient mice and acquired tolerance to cytotoxic anti-cancer agents.
resultsWe performed a synthetic lethal screening of 1535 annotated chemical compounds, and identified 27 candidates selectively killing the GC cell lines. The most potent drug mestranol, an oestrogen derivative, and other oestrogen receptor modulators specifically attenuated cell viability of the GC cell lines by inducing apoptosis preceded by DNA damage. Moreover, mestranol could significantly suppress tumour growth of the GC cells subcutaneously transplanted into nude mice, consistent with longer survival time in the female DCKO mice than in the male. Expectedly, human E-cadherin-mutant and -low gastric cancer cells showed higher susceptibility to oestrogen drugs in contrast to E-cadherin-intact ones in vitro and in vivo.
conclusionsThese findings may lead to the development of novel therapeutic strategies targeting DGC.
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