ArticleDisease models & mechanisms2025
Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition.
Article in Disease models & mechanisms, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mass spectrometry-based human spatial omics: fundamentals, innovations, and applications.Journal of biomedical science · 2026Pooled it
- Evaluating Batch Correction Methods for Large-Scale Mass Spectrometry Imaging of Heterogeneous Tissues.Analytical chemistry · 2026Article
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17 authors.
Funding
Abstract
The PI3K-mTOR-AKT pathway regulates tumour proliferation, gene expression and metabolism, but pathway inhibition induces heterogeneous feedback reactivation, limiting anti-tumour responses. Measuring heterogeneity of pathway inhibition in tissues using protein biomarker phosphorylation or location is challenging. An integrated multi-modal imaging workflow was developed to assess the heterogeneity of AZD2014 (mTORC1/2 inhibitor) response in a PTEN-null renal cancer model. Spatial responses of metabolite biomarkers were analysed by mass spectrometry imaging (MSI). Control and treated tumours were classified according to metabolite-defined regions enriched in control versus AZD2014-treated tumours, respectively. Noticeably, AZD2014-treated tumours retained regions similar to regions dominant in untreated tumours. Imaging mass cytometry analysis of protein biomarkers in 'control-like' regions following AZD2014 treatment showed reduced phospho-S6, indicating suppression, but retained high expression of the glucose transporter GLUT1. Increasing PI3K-AKT inhibition by combining with AZD8186 (PI3Kβ inhibitor) further decreased the control-like metabolic signature, showing PI3K-dependent resistance. This demonstrates that MSI-based workflows yield novel insights into the pharmacodynamic effects of mTORC1/2 inhibition in tumours, which classical biomarkers do not resolve. Coupling these workflows with spatial-omics approaches can deliver greater insights into heterogeneity of treatment response.
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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.