ArticleCancers2019
Synergistic Anti-Tumor Effect of mTOR Inhibitors with Irinotecan on Colon Cancer Cells.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Rapamycin suppresses small bowel adenocarcinoma HUTU 80 cells proliferation by inhibiting hypoxia-inducible factor-1α mediated metabolic reprogramming.World journal of gastrointestinal oncology · 2025Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Endophytic fungi as a potential source of anti-cancer drug.Archives of microbiology · 2024Review
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Oxyresveratrol Alleviates Irinotecan-Induced Diarrhea and Enhances Antitumor Effects in Colorectal Cancer.Drug design, development and therapy · 2024Article
- The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.International journal of biological sciences · 2024Article
- Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells.Natural products and bioprospecting · 2023Article
- Hypothesis: functional age and onset of autosomal dominant genetic prion disease.Theory in biosciences = Theorie in den Biowissenschaften · 2023Article
- Review
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- The emerging era of personalized medicine in advanced colorectal cancer.Journal of gastroenterology and hepatology · 2022Review
- Article
- Inhibition of Heme Export and/or Heme Synthesis Potentiates Metformin Anti-Proliferative Effect on Cancer Cell Lines.Cancers · 2022Article
- Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93.Frontiers in microbiology · 2022Article
- Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer.World journal of gastrointestinal oncology · 2021Review
- Article
- [Cytotoxic effect of photodynamic liposome gel combined with trastuzumab on drugresistant breast cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression.Biomedicines · 2021Review
- Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Advanced colorectal cancer has a poor prognosis because of metastasis formation and resistance to combined therapies. Downstream of PI3K/Akt and Ras/MAPK pathways, the mTOR kinase plays a decisive role in treatment failure. We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. Thus, we hypothesized that the complete inhibition of the PI3K/AKT/mTOR/HIF-1α axis with mTOR catalytic inhibitors and low doses of irinotecan may have antitumor effects. We showed that the AZD8055 and AZD2014 inhibitors were much more potent than rapamycin to reduce cell viability of four colon cell lines. On the other hand, whereas AZD2014 alone inhibits migration by 40%, the drug combination led to 70% inhibition. Similarly, neither irinotecan nor AZD2014 significantly reduced cell invasion, whereas a combination of the two inhibits invasion by 70%. In vivo, irinotecan and AZD2014 combination drastically reduced ectopic patient-derived colon tumor growth and this combination was more potent than Folfox or Folfiri. Finally, the combination totally inhibited liver and lung metastases developed from orthotopic implantation of SW480 cells. Thus, the use of mTOR catalytic inhibitors, in association with other chemotherapeutic agents like irinotecan at low doses, is potentially a hope for colon cancer treatment.
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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.