ArticleClinical and translational medicine2024
PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- PTBP1-Mediated Alternative Splicing of DNAJB6 Promotes Everolimus Resistance in Clear Cell Renal Cell Carcinoma via EIF4B/PKIB/AKT/mTOR Positive Feedback Loop.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Therapeutic Vulnerabilities of the Key Genetic Drivers in Leiomyosarcoma.Medical sciences (Basel, Switzerland) · 2026Review
- A Review of Proteomic Studies in Uterine Leiomyosarcoma: Biomarkers, Pathways, and Clinical Potential.Current issues in molecular biology · 2026Review
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas.Journal for immunotherapy of cancer · 2026Article
- Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026Review
- PIK3R1 as a Gastric Cancer Biomarker Linked to CD73Oncology research · 2026Article
- Review
- MicroRNAs in Uterine Leiomyosarcoma: From Molecular Mechanisms to Clinical Applications.International journal of molecular sciences · 2025Review
- Facilitation of natural killer T-cell cytotoxic activity in uterine sarcoma via theTranslational cancer research · 2025Article
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- Humanized patient-derived xenograft mouse model bearing ovarian clear cell carcinoma.Journal of gynecologic oncology · 2025Article
- Review
- Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lung cancer tumor immune microenvironment: analyzing immune escape mechanisms and exploring emerging therapeutic targets.Frontiers in immunology · 2025Review
- Single-cell profiling delineates the tumor microenvironment and immunological networks in patient-derived uterine leiomyosarcoma.Frontiers in immunology · 2025Article
- Dual Inhibition of PI3 Kinase and MAP Kinase Signaling Pathways in Intrahepatic Cholangiocellular Carcinoma Cell Lines Leads to Proliferation Arrest but Not Apoptosis.Current issues in molecular biology · 2024Article
- PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6Clinical and translational medicine · 2024Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
backgroundUterine leiomyosarcomas (uLMS) are aggressive tumours with poor prognosis and limited treatment options. Although immune checkpoint blockade (ICB) has proven effective in some 'challenging-to-treat' cancers, clinical trials showed that uLMS do not respond to ICB. Emerging evidence suggests that aberrant PI3K/mTOR signalling can drive resistance to ICB. We therefore explored the relevance of the PI3K/mTOR pathway for ICB treatment in uLMS and explored pharmacological inhibition of this pathway to sensitise these tumours to ICB.
methodsWe performed an integrated multiomics analysis based on TCGA data to explore the correlation between PI3K/mTOR dysregulation and immune infiltration in 101 LMS. We assessed response to PI3K/mTOR inhibitors in immunodeficient and humanized uLMS patient-derived xenografts (PDXs) by evaluating tumour microenvironment modulation using multiplex immunofluorescence. We explored response to single-agent and a combination of PI3K/mTOR inhibitors with PD-1 blockade in humanized uLMS PDXs. We mapped intratumoural dynamics using single-cell RNA/TCR sequencing of serially collected biopsies.
resultsPI3K/mTOR over-activation (pS6
conclusionsOur findings indicate that aberrant PI3K/mTOR pathway activation contributes to immune escape in uLMS and provides a rationale for combining PI3K/mTOR inhibition with ICB for the treatment of this patient population.
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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.