ArticleBritish journal of cancer2013
Acquired resistance to temsirolimus in human renal cell carcinoma cells is mediated by the constitutive activation of signal transduction pathways through mTORC2.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Review
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- Expression of TXNIP is associated with angiogenesis and postoperative relapse of conventional renal cell carcinoma.Scientific reports · 2021Article
- Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities.Nature reviews. Urology · 2019Review
- The Effects of Different mTOR Inhibitors in EGFR Inhibitor Resistant Colon Carcinoma Cells.Pathology oncology research : POR · 2019Article
- Pan-class I PI3-kinase inhibitor BKM120 induces MEK1/2-dependent mitotic catastrophe in non-Hodgkin lymphoma leading to apoptosis or polyploidy determined by Bax/Bak and p53.Cell death & disease · 2018Article
- Dual targeting of mitochondrial function and mTOR pathway as a therapeutic strategy for diffuse intrinsic pontine glioma.Oncotarget · 2018Article
- Cancer Metabolism: a Hope for Curing Cancer.Biomolecules & therapeutics · 2018Article
- Article
- Promising response to axitinib rechallenge for metastatic renal cell carcinoma after progression on prior axitinib: report of two cases.International cancer conference journal · 2018Article
- Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.Targeted oncology · 2017Review
- Molecular mechanism mediating cytotoxic activity of axitinib in sunitinib-resistant human renal cell carcinoma cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
- Article
- Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.Molecular cancer · 2015Review
- Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma.British journal of cancer · 2015Article
- Enhanced sensitivity to sorafenib by inhibition of Akt1 expression in human renal cell carcinoma ACHN cells both in vitro and in vivo.Human cell · 2015Article
- Dual Targeting of mTOR Activity with Torin2 Potentiates Anticancer Effects of Cisplatin in Epithelial Ovarian Cancer.Molecular medicine (Cambridge, Mass.) · 2015Article
- Mammalian Target of Rapamycin Inhibitors Resistance Mechanisms in Clear Cell Renal Cell Carcinoma.Current signal transduction therapy · 2014Article
- Cross-communication between histone H3 and H4 acetylation and Akt-mTOR signalling in prostate cancer cells.Journal of cellular and molecular medicine · 2014Article
- HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in vitro by diminishing cdk2 and cyclin A.Molecular cancer · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe objective of this study was to characterise the mechanism underlying acquired resistance to temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), in renal cell carcinoma (RCC).
methodsA parental human RCC cell line, ACHN (ACHN/P), was continuously exposed to increasing doses of up to 20 μM of temsirolimus, and a cell line resistant to temsirolimus (ACHN/R), showing a sixfold higher IC50 than that of ACHN/P, was developed.
resultsFollowing treatment with temsirolimus, phosphorylation of S6 kinase in ACHN/P was markedly inhibited, whereas there was no detectable expression of phosphorylated S6 in ACHN/R before and after temsirolimus treatment. However, AKT and p44/42 mitogen-activated protein kinase (MAPK) were constitutively phosphorylated even after temsirolimus treatment in ACHN/R, but not in ACHN/P. There was no significant difference between the sensitivities of ACHN/P and ACHN/R to KU0063794, a dual inhibitor of mTOR complex 1 (mTORC1) and mTORC2. Similar sensitivities to temsirolimus in ACHN/P and ACHN/R could be achieved by additional treatment with specific inhibitors of AKT- and MAPK-signaling pathways.
conclusionThe activation of signal transduction pathways via mTORC2, but not via mTORC1, may have an important role in the acquisition of a resistant phenotype to temsirolimus in RCC.
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