ArticleProceedings of the National Academy of Sciences of the United States of America2008
Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- A bibliometric and visual analysis of the impact of senescence on tumor immunotherapy.Frontiers in immunology · 2025Pooled it
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- Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- BCL-2 Family Inhibition Enhances mTORC1/2 Inhibition in PIK3CA-Mutant Colorectal Cancer.Molecular cancer therapeutics · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- Wnt Signaling Pathway in Tumor Biology.Genes · 2024Review
- Successful treatment of juvenile polyposis of infancy with sirolimus: a case report.BMC pediatrics · 2024Article
- Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention.Journal of translational medicine · 2024Article
- Chemoprevention in Inherited Colorectal Cancer Syndromes.Clinics in colon and rectal surgery · 2024Review
- Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer.Gynecologic oncology reports · 2024Article
- Review
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- Cancer prevention with rapamycin.Oncotarget · 2023Article
- Traditional Chinese medicine for colorectal cancer treatment: potential targets and mechanisms of action.Chinese medicine · 2023Review
- A Review of the Clinical Presentation, Outcomes, and Treatments of Patients Having Desmoid Tumors.Gastro hep advances · 2023Review
- Effect of rapamycin on aging and age-related diseases-past and future.GeroScience · 2021Review
- Rapamycin Extends Life Span in ApcClinical colorectal cancer · 2021Article
- Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth via mTOR complex 1 (mTORC1), whose activation has been implicated in many human cancers. However, mTORC1's status in gastrointestinal tumors has not been characterized thoroughly. We have found that the mTORC1 pathway is activated with increased expression of the mTOR protein in intestinal polyps of the Apc(Delta716) heterozygous mutant mouse, a model for human familial adenomatous polyposis. An 8-week treatment with RAD001 (everolimus) suppressed the mTORC1 activity in these polyps and inhibited proliferation of the adenoma cells as well as tumor angiogenesis, which significantly reduced not only the number of polyps but also their size. beta-Catenin knockdown in the colon cancer cell lines reduced the mTOR level and thereby inhibited the mTORC1 signaling. These results suggest that the Wnt signaling contributes to mTORC1 activation through the increased level of mTOR and that the activation plays important roles in the intestinal polyp formation and growth. Indeed, long-term RAD001 treatment significantly reduced mortality of the Apc(Delta716) mice. Thus, we propose that the mTOR inhibitors may be efficacious for therapy and prevention of colonic adenomas and cancers with Wnt signaling activation.
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