biostudies-literatureWitzig TENCI NIH HHS328-35https://www.ebi.ac.uk/biostudies/studies/S-EPMC4504947biostudies-literatureUnknown126(3)Everolimus is an oral agent that targets the mammalian target of rapamycin (mTOR) pathway. This study investigated mTOR pathway activation in T-cell lymphoma (TCL) cell lines and assessed antitumor activity in patients with relapsed/refractory TCL in a phase 2 trial. The mTOR pathway was activated in all 6 TCL cell lines tested and everolimus strongly inhibited malignant T-cell proliferation with minimal cytotoxic effects. Everolimus completely inhibited phosphorylation of ribosomal S6, a raptor/mTOR complex 1 (mTORC1) target, without a compensatory activation of the rictor/mTORC2 target Akt (S475). In the clinical trial, 16 patients with relapsed TCL were enrolled and received everolimus 10 mg by mouth daily. Seven patients (44%) had cutaneous (all mycosis fungoides); 4 (25%) had peripherBloodThe mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma.PMC4504947P30 CA015083CA127433R01 CA127433CA97274P50 CA097274Habermann TMMacon WJohnston PBPorrata LFNowakowski GSInwards DJColgan JPWitzig TEHan JJAnsell SMLaPlant BMicallef INTun HWReeder CGupta MStenson MMarkovic SfalseThe mTORC1 inhibitor everolimus has antitumor activity in vitro and produces tumor responses in patients with relapsed T-cell lymphoma.Everolimus is an oral agent that targets the mammalian target of rapamycin (mTOR) pathway. This study investigated mTOR pathway activation in T-cell lymphoma (TCL) cell lines and assessed antitumor activity in patients with relapsed/refractory TCL in a phase 2 trial. The mTOR pathway was activated in all 6 TCL cell lines tested and everolimus strongly inhibited malignant T-cell proliferation with minimal cytotoxic effects. Everolimus completely inhibited phosphorylation of ribosomal S6, a raptor/mTOR complex 1 (mTORC1) target, without a compensatory activation of the rictor/mTORC2 target Akt (S475). In the clinical trial, 16 patients with relapsed TCL were enrolled and received everolimus 10 mg by mouth daily. Seven patients (44%) had cutaneous (all mycosis fungoides); 4 (25%) had peripher2015-01-01T00:00:00Z2015 Jul2025-04-04T21:52:02.394Z2019-03-27T01:55:14ZS-EPMC45049472592105910.1182/blood-2015-02-629543