ArticleOncogene2017
Tumor microenvironment confers mTOR inhibitor resistance in invasive intestinal adenocarcinoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- LRRC32 Mediates Resistance to Everolimus in Hormone Receptor-Positive, HER2-Negative Breast Cancer.Cancer management and research · 2026Article
- Article
- TGF-β signaling promotes desmoid tumor formation via CSRP2 upregulation.Cancer science · 2024Article
- Loss of Dok-3 in Non-tumor Cells Induces Malignant Transformation of Benign Epithelial Tumor Cells of the Intestine.Cancer research communications · 2022Article
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer.Journal of Cancer · 2022Review
- Lactate-related metabolic reprogramming and immune regulation in colorectal cancer.Frontiers in endocrinology · 2022Review
- A Review: PI3K/AKT/mTOR Signaling Pathway and Its Regulated Eukaryotic Translation Initiation Factors May Be a Potential Therapeutic Target in Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2022Review
- Ipriflavone Suppresses Growth of Esophageal Squamous Cell Carcinoma Through Inhibiting mTORFrontiers in oncology · 2021Article
- Synthetic lethality between MyD88 loss and mutations in Wnt/β-catenin pathway in intestinal tumor epithelial cells.Oncogene · 2021Article
- Rapamycin and trametinib: a rational combination for treatment of NSCLC.International journal of biological sciences · 2021Article
- RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1.Cancer medicine · 2020Article
- miRNA-based biomarkers, therapies, and resistance in Cancer.International journal of biological sciences · 2020Review
- Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.Oncoimmunology · 2020Article
- Predicting associations among drugs, targets and diseases by tensor decomposition for drug repositioning.BMC bioinformatics · 2019Article
- Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Review
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- miR-1271 enhances the sensitivity of colorectal cancer cells to cisplatin.Experimental and therapeutic medicine · 2019Article
- Complex interplay between tumor microenvironment and cancer therapy.Frontiers of medicine · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is frequently activated in cancers and can be counteracted with the clinical mTORC1 inhibitors everolimus and temsirolimus. Although mTORC1 and dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. Using the cis-Apc/Smad4 mouse model of locally invasive intestinal adenocarcinoma, we show that administration of everolimus or the dual mTORC1/2 inhibitor AZD8055 significantly reduces the growth of intestinal tumors. In contrast, although everolimus treatment at earlier phase of tumor progression delayed invasion of the tumors, both inhibitors exhibited little effect on blocking invasion of the tumors when administered later in their progression. Biochemical and immunohistochemical analyses revealed that treatment of cis-Apc/Smad4 mice with everolimus or AZD8055 induced marked increases in epidermal growth factor receptor (EGFR) and MEK/ERK signaling in tumor epithelial and stromal cells, respectively. Notably, co-administration of AZD8055 and the EGFR inhibitor erlotinib or the MEK inhibitor trametinib was sufficient to suppress tumor invasion in cis-Apc/Smad4 mice. These data indicate that mTOR inhibitor resistance in invasive intestinal tumors involves feedback signaling from both cancer epithelial and stromal cells, highlighting the role of tumor microenvironment in drug resistance, and support that simultaneous inhibition of mTOR and EGFR or MEK may be more effective in treating colon cancer.
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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.