{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T22:48:18Z","timestamp":1793486898489,"version":"4.5.0"},"reference-count":66,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-18-1-0370"],"award-info":[{"award-number":["W81XWH-18-1-0370"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["R35-CA197459"],"award-info":[{"award-number":["R35-CA197459"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["P01-CA120964"],"award-info":[{"award-number":["P01-CA120964"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["T32-ES016645"],"award-info":[{"award-number":["T32-ES016645"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019364","name":"Revolution Medicines","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008126","name":"Dana-Farber\/Harvard Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008126","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NIH 5 P30 CA06516"],"award-info":[{"award-number":["NIH 5 P30 CA06516"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.isci.2022.105458","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T19:25:21Z","timestamp":1666985121000},"page":"105458","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex"],"prefix":"10.1016","volume":"25","author":[{"given":"Molly C.","family":"McNamara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Hosios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Torrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Henske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Lee","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher A.","family":"Sarosiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Valvezan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-5956","authenticated-orcid":false,"given":"Brendan D.","family":"Manning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2022.105458_bib1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.trecan.2016.03.008","article-title":"Emerging role of mTOR in the response to cancer therapeutics","volume":"2","author":"Ilagan","year":"2016","journal-title":"Trends Cancer"},{"key":"10.1016\/j.isci.2022.105458_bib2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41556-018-0205-1","article-title":"mTOR as a central hub of nutrient signalling and cell growth","volume":"21","author":"Kim","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.isci.2022.105458_bib3","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cell.2017.03.035","article-title":"mTOR signaling in growth, metabolism, and disease","volume":"169","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.isci.2022.105458_bib4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"Ben-Sahra","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.isci.2022.105458_bib5","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2016.35","article-title":"Tuberous sclerosis complex","volume":"2","author":"Henske","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.isci.2022.105458_bib6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev-genom-083118-015354","article-title":"Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex","volume":"20","author":"Salussolia","year":"2019","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"10.1016\/j.isci.2022.105458_bib7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/path.4176","article-title":"TSC1 involvement in bladder cancer: diverse effects and therapeutic implications","volume":"230","author":"Guo","year":"2013","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.isci.2022.105458_bib8","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1136\/gutjnl-2016-312734","article-title":"TSC1\/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication","volume":"66","author":"Ho","year":"2017","journal-title":"Gut"},{"key":"10.1016\/j.isci.2022.105458_bib9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1042\/bst0310597","article-title":"Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours","volume":"31","author":"Knowles","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"10.1016\/j.isci.2022.105458_bib10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tips.2014.11.004","article-title":"Current treatment strategies for inhibiting mTOR in cancer","volume":"36","author":"Chiarini","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.isci.2022.105458_bib11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: one drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab"},{"key":"10.1016\/j.isci.2022.105458_bib12","doi-asserted-by":"crossref","first-page":"106037","DOI":"10.1016\/j.phrs.2021.106037","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: a 2022 update","volume":"175","author":"Roskoski","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.isci.2022.105458_bib13","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1371\/journal.pbio.1000038","article-title":"Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2","volume":"7","author":"Feldman","year":"2009","journal-title":"PLoS Biol."},{"key":"10.1016\/j.isci.2022.105458_bib14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13045-019-0754-1","article-title":"Targeting mTOR for cancer therapy","volume":"12","author":"Hua","year":"2019","journal-title":"J.\u00a0Hematol. Oncol."},{"key":"10.1016\/j.isci.2022.105458_bib15","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1042\/CS20171158","article-title":"Drug discovery targeting the mTOR pathway","volume":"132","author":"Martelli","year":"2018","journal-title":"Clin. Sci. (Lond.)"},{"key":"10.1016\/j.isci.2022.105458_bib16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1750-1172-7-87","article-title":"Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial","volume":"7","author":"Cabrera-Lopez","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.isci.2022.105458_bib17","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/ana.20784","article-title":"Rapamycin causes regression of astrocytomas in tuberous sclerosis complex","volume":"59","author":"Franz","year":"2006","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.isci.2022.105458_bib18","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMoa1100391","article-title":"Efficacy and safety of sirolimus in lymphangioleiomyomatosis","volume":"364","author":"McCormack","year":"2011","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.isci.2022.105458_bib19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/path.4827","article-title":"New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex","volume":"241","author":"Lam","year":"2017","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.isci.2022.105458_bib20","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa063564","article-title":"Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis","volume":"358","author":"Bissler","year":"2008","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.isci.2022.105458_bib21","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.98674","article-title":"TSC2-deficient tumors have evidence of T\u00a0cell exhaustion and respond to anti-PD-1\/anti-CTLA-4 immunotherapy","volume":"3","author":"Liu","year":"2018","journal-title":"JCI Insight"},{"key":"10.1016\/j.isci.2022.105458_bib22","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.135071","article-title":"IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex","volume":"5","author":"Valvezan","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.isci.2022.105458_bib23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41580-018-0089-8","article-title":"Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins","volume":"20","author":"Singh","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.isci.2022.105458_bib24","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev-cancerbio-050216-121933","article-title":"Apoptosis and cancer","volume":"1","author":"Letai","year":"2017","journal-title":"Annu. Rev. Cancer Biol."},{"key":"10.1016\/j.isci.2022.105458_bib25","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1111\/febs.13714","article-title":"Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise","volume":"283","author":"Sarosiek","year":"2016","journal-title":"FEBS J."},{"key":"10.1016\/j.isci.2022.105458_bib26","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1158\/1535-7163.MCT-13-0058","article-title":"BH3 mimetics: status of the field and new developments","volume":"12","author":"Billard","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.isci.2022.105458_bib27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1172\/JCI28281","article-title":"Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737","volume":"117","author":"Del Gaizo Moore","year":"2007","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.isci.2022.105458_bib28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ccr.2007.07.001","article-title":"BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents","volume":"12","author":"Deng","year":"2007","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2022.105458_bib29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ccr.2006.10.006","article-title":"Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia","volume":"10","author":"Konopleva","year":"2006","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2022.105458_bib30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrc2615","article-title":"Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics","volume":"9","author":"Cragg","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2022.105458_bib31","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.ccell.2018.11.004","article-title":"BH3-Mimetic drugs: blazing the trail for new cancer medicines","volume":"34","author":"Merino","year":"2018","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2022.105458_bib32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s13046-021-02157-5","article-title":"BH3-mimetics: recent developments in cancer therapy","volume":"40","author":"Townsend","year":"2021","journal-title":"J.\u00a0Exp. Clin. Cancer Res."},{"key":"10.1016\/j.isci.2022.105458_bib33","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mito.2014.04.011","article-title":"Synthetic lethality by co-targeting mitochondrial apoptosis and PI3K\/Akt\/mTOR signaling","volume":"19","author":"Fulda","year":"2014","journal-title":"Mitochondrion"},{"key":"10.1016\/j.isci.2022.105458_bib34","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.1158\/1078-0432.CCR-09-0589","article-title":"Combined Bcl-2\/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model","volume":"15","author":"Kim","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.isci.2022.105458_bib35","doi-asserted-by":"crossref","first-page":"E1288","DOI":"10.1073\/pnas.1411848112","article-title":"Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer","volume":"112","author":"Faber","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2022.105458_bib36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41419-017-0169-2","article-title":"Downregulation of MCL-1 and upregulation of PUMA using mTOR inhibitors enhance antitumor efficacy of BH3 mimetics in triple-negative breast cancer","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.isci.2022.105458_bib37","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1158\/1541-7786.MCR-13-0650","article-title":"PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD","volume":"12","author":"Pareja","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"10.1016\/j.isci.2022.105458_bib38","doi-asserted-by":"crossref","first-page":"35287","DOI":"10.1074\/jbc.M113.495986","article-title":"Pan-mammalian target of rapamycin (mTOR) inhibitor AZD8055 primes rhabdomyosarcoma cells for ABT-737-induced apoptosis by down-regulating Mcl-1 protein","volume":"288","author":"Preuss","year":"2013","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.isci.2022.105458_bib39","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1158\/1535-7163.MCT-08-0268","article-title":"ABT-263 and rapamycin act cooperatively to kill lymphoma cells in\u00a0vitro and in\u00a0vivo","volume":"7","author":"Ackler","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.isci.2022.105458_bib40","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1158\/0008-5472.CAN-13-3460","article-title":"Rapamycin rescues ABT-737 efficacy in small cell lung cancer","volume":"74","author":"Gardner","year":"2014","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2022.105458_bib41","doi-asserted-by":"crossref","first-page":"32089","DOI":"10.18632\/oncotarget.5156","article-title":"Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia","volume":"6","author":"Iacovelli","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.isci.2022.105458_bib42","doi-asserted-by":"crossref","first-page":"38099","DOI":"10.18632\/oncotarget.17485","article-title":"Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R","volume":"8","author":"Filippakis","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.isci.2022.105458_bib43","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/0092-8674(92)90643-Q","article-title":"Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases","volume":"69","author":"Chung","year":"1992","journal-title":"Cell"},{"key":"10.1016\/j.isci.2022.105458_bib44","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1158\/1535-7163.MCT-15-0365","article-title":"AZD2014, an inhibitor of mTORC1 and mTORC2, is highly effective in ER+ breast cancer when administered using intermittent or continuous schedules","volume":"14","author":"Guichard","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.isci.2022.105458_bib45","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature17963","article-title":"Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor","volume":"534","author":"Rodrik-Outmezguine","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.isci.2022.105458_bib46","doi-asserted-by":"crossref","first-page":"8023","DOI":"10.1074\/jbc.M900301200","article-title":"An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1","volume":"284","author":"Thoreen","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.isci.2022.105458_bib47","doi-asserted-by":"crossref","first-page":"e1006242","DOI":"10.1371\/journal.pgen.1006242","article-title":"Whole exome sequencing identifies TSC1\/TSC2 biallelic loss as the primary and sufficient driver event for renal angiomyolipoma development","volume":"12","author":"Giannikou","year":"2016","journal-title":"PLoS Genet."},{"key":"10.1016\/j.isci.2022.105458_bib48","doi-asserted-by":"crossref","first-page":"6192","DOI":"10.1074\/jbc.M610643200","article-title":"Rapid turnover of mcl-1 couples translation to cell survival and apoptosis","volume":"282","author":"Adams","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.isci.2022.105458_bib49","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3324\/haematol.2016.159160","article-title":"Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas","volume":"102","author":"Bi","year":"2017","journal-title":"Haematologica"},{"key":"10.1016\/j.isci.2022.105458_bib50","doi-asserted-by":"crossref","first-page":"10853","DOI":"10.1073\/pnas.0804821105","article-title":"mTORC1 promotes survival through translational control of Mcl-1","volume":"105","author":"Mills","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2022.105458_bib51","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1101\/gad.1604407","article-title":"Dissecting eIF4E action in tumorigenesis","volume":"21","author":"Wendel","year":"2007","journal-title":"Genes Dev."},{"key":"10.1016\/j.isci.2022.105458_bib52","doi-asserted-by":"crossref","first-page":"17414","DOI":"10.1073\/pnas.0809136105","article-title":"Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation","volume":"105","author":"Choo","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.isci.2022.105458_bib53","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature03205","article-title":"Regulation of cap-dependent translation by eIF4E inhibitory proteins","volume":"433","author":"Richter","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.isci.2022.105458_bib54","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.canlet.2014.03.001","article-title":"PI3K\/mTOR dual inhibitor NVP-BEZ235 decreases Mcl-1 expression and sensitizes ovarian carcinoma cells to Bcl-xL-targeting strategies, provided that Bim expression is induced","volume":"348","author":"Jebahi","year":"2014","journal-title":"Cancer Lett."},{"key":"10.1016\/j.isci.2022.105458_bib55","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fonc.2012.00121","article-title":"Shifting the balance of mitochondrial apoptosis: therapeutic perspectives","volume":"2","author":"Fulda","year":"2012","journal-title":"Front. Oncol."},{"key":"10.1016\/j.isci.2022.105458_bib56","doi-asserted-by":"crossref","first-page":"212574","DOI":"10.7573\/dic.212574","article-title":"Venetoclax: evidence to date and clinical potential","volume":"8","author":"Juarez-Salcedo","year":"2019","journal-title":"Drugs Context"},{"key":"10.1016\/j.isci.2022.105458_bib57","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1200\/JCO.2010.31.6208","article-title":"Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors","volume":"29","author":"Gandhi","year":"2011","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.isci.2022.105458_bib58","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1038\/s41591-019-0668-z","article-title":"A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity","volume":"25","author":"Khan","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.isci.2022.105458_bib59","doi-asserted-by":"crossref","first-page":"6896","DOI":"10.1038\/s41467-021-27210-x","article-title":"Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity","volume":"12","author":"Lv","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.isci.2022.105458_bib60","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1172\/JCI200317222","article-title":"Loss of Tsc1\/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR","volume":"112","author":"Zhang","year":"2003","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.isci.2022.105458_bib61","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.1128\/MCB.00289-08","article-title":"The TSC1-TSC2 complex is required for proper activation of mTOR complex 2","volume":"28","author":"Huang","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.isci.2022.105458_bib62","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.devcel.2006.10.007","article-title":"Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1","volume":"11","author":"Guertin","year":"2006","journal-title":"Dev. Cell"},{"key":"10.1016\/j.isci.2022.105458_bib63","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1093\/bioinformatics\/btaa102","article-title":"SynergyFinder: a web application for analyzing drug combination dose-response matrix data","volume":"36","author":"Ianevski","year":"2020","journal-title":"Bioinformatics"},{"key":"10.1016\/j.isci.2022.105458_bib64","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.isci.2022.105458_bib65","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/path.5921","article-title":"Developing image analysis methods for digital pathology","volume":"257","author":"Bankhead","year":"2022","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.isci.2022.105458_bib66","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.63326","article-title":"The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals","volume":"10","author":"Torrence","year":"2021","journal-title":"Elife"}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004222017308?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004222017308?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:56:48Z","timestamp":1778900208000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004222017308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":66,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["S2589004222017308"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2022.105458","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2022.105458","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s).","name":"copyright","label":"Copyright"}],"article-number":"105458"}}