ArticlePloS one2013
Combination of mTOR and EGFR kinase inhibitors blocks mTORC1 and mTORC2 kinase activity and suppresses the progression of colorectal carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 16 papers.
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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.
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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
16 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer.Journal of gastrointestinal oncology · 2021Article
- Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation.International journal of molecular sciences · 2021Review
- Gefitinib Results in Robust Host-Directed Immunity AgainstFrontiers in immunology · 2021Article
- Co-targeting EGFR and mTOR with gefitinib and everolimus in triple-negative breast cancer cells.Scientific reports · 2020Article
- mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy.Oncogene · 2018Article
- Tumor microenvironment confers mTOR inhibitor resistance in invasive intestinal adenocarcinoma.Oncogene · 2017Article
- The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases.Molecules (Basel, Switzerland) · 2017Article
- Hepatitis B Virus X Protein and Hepatocarcinogenesis.International journal of molecular sciences · 2016Review
- Posttranslational modifications of FOXO1 regulate epidermal growth factor receptor tyrosine kinase inhibitor resistance for non-small cell lung cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Combination of cetuximab and PP242 synergistically suppress the progression of wild-type KRAS colorectal carcinoma.OncoTargets and therapy · 2015Article
- mTOR pathway: A current, up-to-date mini-review (Review).Oncology letters · 2014Article
- A phase I trial of everolimus in combination with 5-FU/LV, mFOLFOX6 and mFOLFOX6 plus panitumumab in patients with refractory solid tumors.Cancer chemotherapy and pharmacology · 2014Article
- PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis.Oncology letters · 2014Article
- mTOR pathway in colorectal cancer: an update.Oncotarget · 2014Review
- Glial progenitors as targets for transformation in glioma.Advances in cancer research · 2014Review
Corrections and comments
- Retraction · 2025-08-26Concerns/Issues about Animal Welfare · Concerns/Issues about Image · Concerns/Issues about Methods · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · · See also: https://pubpeer.com/publications/0CA417CE7AD3B5DDA349EF7FEB0C34
- Retracted
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. The second generation of mTOR inhibitors such as PP242 targets mTOR kinase; thus, they are capable of inhibiting both mTORC1 and mTORC2. To examine the therapeutic potential of the mTOR kinase inhibitors, we treated a panel of colorectal carcinoma cell lines with PP242. Western blotting showed that the PP242 inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKT(S473)) was transient only in the first few hours of the PP242 treatment. Receptor tyrosine kinase arrays further revealed that PP242 treatment increased the phosphorylated epidermal growth factor receptor (EGFR) at Tyr 1068 (EGFR(T1068)). The parallel increase of AKT(S473) and EGFR(T1068) in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2. To test this notion, we showed that the combination of PP242 with erlotinib, an EGFR small molecule inhibitor, blocked both mTORC1 and mTORC2 kinase activity. In addition, we showed that the combination treatment inhibited colony formation, blocked cell growth and induced apoptotic cell death. A systemic administration of PP242 and erlotinib resulted in the progression suppression of colorectal carcinoma xenografts in mice. This study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma.
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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.