ArticleBritish journal of cancer2025
AKT/mTOR as a targetable hub to overcome multimodal resistance to EGFR inhibitors in oesophageal squamous cell carcinoma.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Antibody-Drug Conjugates in the Treatment of Esophageal Cancer.Current treatment options in oncology · 2026Review
- WDR72 Drives Esophageal Squamous Cell Carcinoma Progression by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Advances in esophageal organoids: from construction to applications.Journal of tissue engineeringReview
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Authors and funding
15 authors.
Funding
Abstract
backgroundOesophageal squamous cell carcinoma (ESCC) is associated with late-stage diagnosis, limited treatment options, the development of drug resistance and poor outcome. Epidermal growth factor receptor is frequently dysregulated in ESCC. EGFR copy number gain and/or protein overexpression are beneficial as predictive biomarkers for EGFR inhibitor therapy; however, inherent and acquired resistance limit response rates, and durable disease control is infrequent.
methodsThis study investigates the causes of resistance to the off-patent EGFR inhibitor gefitinib in three gefitinib-resistance model systems: intrinsic, acquired resistance and growth factor (TGFβ)-induced resistance. Findings from studies in 13 ESCC cell lines were validated in tumour specimens from the GO2 clinical trial (n = 32), publicly available ESCC datasets (n = 264), cell line-derived xenograft (CDX) and patient-derived organoid (PDO) model systems.
resultsGefitinib resistance in ESCC was associated with diverse mechanisms, including RTK signalling via PDGFRβ and IGFBP3/IGF1/IGF1R, as well as EMT, but was consistently associated with the maintenance of signalling via AKT across multiple cell lines and model systems. AKT or mTOR inhibitors synergised with gefitinib in 2D and anchorage-independent 3D assays. Gefitinib plus the AKT inhibitor capivasertib (Truqap™) was efficacious in human CDX and PDO models. DISCUSSION: Combining AKT/mTOR inhibitors with EGFR inhibitors in EGFR-driven ESCC shows synergism but with elevated toxicity. Monotherapy AKT/mTOR inhibitors or combined therapy at reduced doses could offer improved, cost-effective therapy options for gefitinib-resistant cancer.
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