ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
The ATP-competitive mTOR inhibitor INK128 enhances in vitro and in vivo radiosensitivity of pancreatic carcinoma cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- The Role of PI3K/AKT/mTOR Signaling in Tumor Radioresistance and Advances in Inhibitor Research.International journal of molecular sciences · 2025Review
- Interplay Between Key Molecular Signaling Pathways and Immune Players Following Brain Irradiation.Mediators of inflammation · 2025Review
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- Inhibition of the Translation Initiation Factor eIF4A Enhances Tumor Cell Radiosensitivity.Molecular cancer therapeutics · 2022Article
- Overview of Research into mTOR Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Translation Initiation Machinery as a Tumor Selective Target for Radiosensitization.International journal of molecular sciences · 2021Review
- The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.Molecular biology reports · 2021Review
- The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.Scientific reports · 2020Article
- Ionizing Radiation and Translation Control: A Link to Radiation Hormesis?International journal of molecular sciences · 2020Review
- Virtual Screening and Optimization of Novel mTOR Inhibitors for Radiosensitization of Hepatocellular Carcinoma.Drug design, development and therapy · 2020Article
- Regulating T Cell Population Alleviates SLE by Inhibiting mTORC1/C2 in MRL/lpr Mice.Frontiers in pharmacology · 2020Article
- Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches.Radiation oncology (London, England) · 2019Review
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- Novel biological strategies to enhance the radiation therapeutic ratio.Radiation oncology journal · 2018Article
- Altering the response to radiation: radiosensitizers and targeted therapies in pancreatic ductal adenocarcinoma: preclinical and emerging clinical evidence.Annals of pancreatic cancer · 2018Article
- The XPO1 Inhibitor Selinexor Inhibits Translation and Enhances the Radiosensitivity of Glioblastoma Cells GrownMolecular cancer therapeutics · 2018Article
- Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.Cellular and molecular life sciences : CMLS · 2018Review
- The Role of the Mammalian Target of Rapamycin (mTOR) in Pulmonary Fibrosis.International journal of molecular sciences · 2018Review
- Exploiting Radiation-Induced Signaling to Increase the Susceptibility of Resistant Cancer Cells to Targeted Drugs: AKT and mTOR Inhibitors as an Example.Molecular cancer therapeutics · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRadiotherapy remains a primary treatment modality for pancreatic carcinoma, a tumor characterized by aberrant mTOR activity. Given the regulatory role of mTOR in gene translation, in this study, we defined the effects of the clinically relevant, ATP-competitive mTOR inhibitor, INK128 on the radiosensitivity of pancreatic carcinoma cell lines. EXPERIMENTAL
designClonogenic survival was used to determine the effects of INK128 on in vitro radiosensitivity of three pancreatic carcinoma cell lines and a normal fibroblast cell line with mTOR activity defined using immunoblots. DNA double-strand breaks were evaluated according to γH2AX foci. The influence of INK128 on radiation-induced gene translation was determined by microarray analysis of polysome-bound mRNA. Leg tumor xenografts grown from pancreatic carcinoma cells were evaluated for mTOR activity, eIF4F cap complex formation, and tumor growth delay.
resultsINK128, while inhibiting mTOR activity in each of the cell lines, enhanced the in vitro radiosensitivity of the pancreatic carcinoma cells but had no effect on normal fibroblasts. The dispersal of radiation-induced γH2AX foci was inhibited in pancreatic carcinoma cells by INK128 as were radiation-induced changes in gene translation. Treatment of mice with INK128 resulted in an inhibition of mTOR activity as well as cap complex formation in tumor xenografts. Whereas INK128 alone had no effect of tumor growth rate, it enhanced the tumor growth delay induced by single and fractionated doses of radiation.
conclusionThese results indicate that mTOR inhibition induced by INK128 enhances the radiosensitivity of pancreatic carcinoma cells and suggest that this effect involves the inhibition of DNA repair.
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