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10.1155/2017/1726078 http://scihub22266oqcxt.onion/10.1155/2017/1726078 C5322438!5322438 !28280521     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28280521 &cmd=llinks): Failed to open stream: HTTP request failed! 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Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity |pdf=|usr=}}{{28280521 }} gab.com Text Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity JO: Oxid Med Cell Longev http://www.kidney.de/pget.php?&tw=1&pmid=28280521 #FOAvip Targeting mTORC1 has been thoroughly explored in cancer therapy. Following encouraging preclinical studies, mTORC1 inhibitors however failed to provide substantial benefits in cancer patients. Several resistance mechanisms have been identified including mutations of mTOR and activation of alternate proliferation pathways. Moreover, emerging evidence discloses intratumoral heterogeneity of mTORC1 activity that further contributes to a reduced anticancer efficacy of mTORC1 inhibitors. Genetic heterogeneity as well as heterogeneous conditions of the tumor environment such as hypoxia profoundly modifies mTORC1 activity in tumors and hence influences the response of tumors to mTORC1 inhibitors. Intriguingly, the heterogeneity of mTORC1 activity also occurs towards its substrates at the single cell level, as mutually exclusive pattern of activation of mTORC1 downstream effectors has been reported in tumors. After briefly describing mTORC1 biology and the use of mTORC1 inhibitors in patients, this review will give an overview on concepts of resistance to mTORC1 inhibition in cancer with a particular focus on intratumoral heterogeneity of mTORC1 activity. Twit Text FOAVip Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity ????Oxid Med Cell Longev http://www.kidney.de/pget.php?&tw=1&pmid=28280521 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28280521 #FOAvip English Wikipedia <ref>{{Cite pmid|28280521 }}</ref> Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity #MMPMID28280521 Faes S ; Demartines N ; Dormond O Oxid Med Cell Longev 2017[]; 2017 (ä): 1726078 PMID28280521 show ga Targeting mTORC1 has been thoroughly explored in cancer therapy. Following encouraging preclinical studies, mTORC1 inhibitors however failed to provide substantial benefits in cancer patients. Several resistance mechanisms have been identified including mutations of mTOR and activation of alternate proliferation pathways. Moreover, emerging evidence discloses intratumoral heterogeneity of mTORC1 activity that further contributes to a reduced anticancer efficacy of mTORC1 inhibitors. Genetic heterogeneity as well as heterogeneous conditions of the tumor environment such as hypoxia profoundly modifies mTORC1 activity in tumors and hence influences the response of tumors to mTORC1 inhibitors. Intriguingly, the heterogeneity of mTORC1 activity also occurs towards its substrates at the single cell level, as mutually exclusive pattern of activation of mTORC1 downstream effectors has been reported in tumors. After briefly describing mTORC1 biology and the use of mTORC1 inhibitors in patients, this review will give an overview on concepts of resistance to mTORC1 inhibition in cancer with a particular focus on intratumoral heterogeneity of mTORC1 activity. |Animals [MESH] |Drug Resistance, Neoplasm/drug effects/*genetics [MESH] |Humans [MESH] |Mechanistic Target of Rapamycin Complex 1 [MESH] |Multiprotein Complexes/*antagonists & inhibitors/*genetics [MESH] |Mutation/*genetics [MESH] |Neoplasms/*drug therapy/enzymology/*genetics [MESH] |Protein Kinase Inhibitors/pharmacology/*therapeutic use [MESH] |Signal Transduction/drug effects [MESH]Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutatio(epmc).pdf DeepDyve Pubget Overpricing