Tian T, Li X, Zhang J. mTOR signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int J Mol Sci. 2019;20:755.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Paplomata E, O’Regan R. The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers. Ther Adv Med Oncol. 2014;6:154–66.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014;4:64.

Article  PubMed  PubMed Central  Google Scholar 

Slomovitz BM, Jiang Y, Yates MS, Soliman PT, Johnston T, Nowakowski M, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol. 2015;33:930–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Majeed ST, Batool A, Majeed R, Bhat NN, Zargar MA, Andrabi KI. mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation. Cell Cycle. 2021;20:839–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13:140–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Buti S, Leonetti A, Dallatomasina A, Bersanelli M. Everolimus in the management of metastatic renal cell carcinoma: an evidence-based review of its place in therapy. Core Evid. 2016;11:23–36.

Article  PubMed  PubMed Central  Google Scholar 

Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fan Y, Sun T, Shao Z, Zhang Q, Ouyang Q, Tong Z, et al. Effectiveness of adding everolimus to the first-line treatment of advanced breast cancer in premenopausal women who experienced disease progression while receiving selective estrogen receptor modulators: a phase 2 randomized clinical trial. JAMA Oncol. 2021;7:e213428.

Article  PubMed  PubMed Central  Google Scholar 

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520–9.

Article  CAS  PubMed  Google Scholar 

Wu X, Xu Y, Liang Q, Yang X, Huang J, Wang J, et al. Recent advances in dual PI3K/mTOR inhibitors for tumour treatment. Front Pharmacol. 2022;13:875372.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mao B, Zhang Q, Ma L, Zhao DS, Zhao P, Yan P. Overview of research into mTOR inhibitors. Molecules. 2022;27:5295.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Owonikoko TK. Inhibitors of mTOR pathway for cancer therapy, moving on from rapalogs to TORKinibs. Cancer. 2015;121:3390–2.

Article  PubMed  Google Scholar 

Sparks CA, Guertin DA. Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene. 2010;29:3733–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ilagan E, Manning BD. Emerging role of mTOR in the response to cancer therapeutics. Trends Cancer. 2016;2:241–51.

Article  PubMed  PubMed Central  Google Scholar 

Ali ES, Mitra K, Akter S, Ramproshad S, Mondal B, Khan IN, et al. Recent advances and limitations of mTOR inhibitors in the treatment of cancer. Cancer Cell Int. 2022;22:284.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, et al. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett. 2013;23:1212–6.

Article  CAS  PubMed  Google Scholar 

Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell. 2006;22:159–68.

Article  CAS  PubMed  Google Scholar 

Oh WJ, Jacinto E. mTOR complex 2 signaling and functions. Cell Cycle. 2011;10:2305–16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mateo J, Olmos D, Dumez H, Poondru S, Samberg NL, Barr S, et al. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. Br J Cancer. 2016;114:889–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Voss MH, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, et al. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer. 2020;123:1590–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Asahina H, Nokihara H, Yamamoto N, Yamada Y, Tamura Y, Honda K, et al. Safety and tolerability of AZD8055 in Japanese patients with advanced solid tumors; a dose-finding phase I study. Invest New Drugs. 2013;31:677–84.

Article  CAS  PubMed  Google Scholar 

Basu B, Dean E, Puglisi M, Greystoke A, Ong M, Burke W, et al. First-in-human pharmacokinetic and pharmacodynamic study of the dual m-TORC 1/2 Inhibitor AZD2014. Clin Cancer Res. 2015;21:3412–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bendell JC, Kelley RK, Shih KC, Grabowsky JA, Bergsland E, Jones S, et al. A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma. Cancer. 2015;121:3481–90.

Article  CAS  PubMed  Google Scholar 

Qian J, Chen Y, Meng T, Ma L, Meng L, Wang X, et al. Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget. 2016;7:67071–86.

Article  PubMed  PubMed Central  Google Scholar 

Zhang Q, Zhang Y, Chen Y, Qian J, Zhang X, Yu K. A Novel mTORC1/2 Inhibitor (MTI-31) inhibits tumor growth, epithelial-mesenchymal transition, metastases, and improves antitumor immunity in preclinical models of lung cancer. Clin Cancer Res. 2019;25:3630–42.

Article  CAS  PubMed  Google Scholar 

Wang X, Meng N, Wang S, Zhang Y, Lu L, Wang R, et al. Non-immunogenic, low-toxicity and effective glioma targeting MTI-31 liposomes. J Control Release. 2019;316:381–92.

Article  CAS  PubMed  Google Scholar 

Wang X, Yue P, Chan CB, Ye K, Ueda T, Watanabe-Fukunaga R, et al. Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation. Mol Cell Biol. 2007;27:7405–13.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tesch H, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, et al. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: results of the single-arm, phase IIIB 4EVER trial. Int J Cancer. 2019;144:877–85.

Article  CAS  PubMed  Google Scholar 

Xu B, Wu Y, Shen L, Ye D, Jappe A, Cherfi A, et al. Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors. J Hematol Oncol. 2011;4:3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shao Z, Cai L, Wang S, Hu X, Shen K, Wang H, et al. 238P BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER+/HER2- advanced breast cancer. Ann Oncol. 2021;32:S463.

Article  Google Scholar 

Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012;485:55–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Powles T, Wheater M, Din O, Geldart T, Boleti E, Stockdale A, et al. A Randomised Phase 2 Study of AZD2014 versus everolimus in patients with VEGF-refractory metastatic clear cell renal cancer. Eur Urol. 2016;69:450–6.

Article  CAS  PubMed  Google Scholar 

Sun SY. mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why? Front Med. 2021;15:221–31.

Article  PubMed