Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou branch, Chang Gung University, Taoyuan 333, Taiwan.
School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Int J Mol Sci. 2019 Jan 24;20(3):500. doi: 10.3390/ijms20030500.
Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of mTOR inhibitors as a future treatment in BTC. Chemotherapy with gemcitabine-based chemotherapy is still the standard of care and no targeted therapy has been established in advanced BTC. PI3K/AKT/mTOR signaling pathway linking to several other pathways and networks regulates cancer proliferation and progression. Emerging evidences reveal mTOR activation is associated with tumorigenesis and drug-resistance in BTC. Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Rapalogs in clinical trials demonstrate some activity in patients with advanced BTC. New-generation mTOR inhibitors against ATP-binding pocket inhibit both TORC1 and TORC2 and demonstrate more potent anti-tumor effects in vitro and in vivo, however, prospective clinical trials are warranted to prove its efficacy in patients with advanced BTC.
患有晚期胆道癌（BTC）的患者，包括胆管癌（CCA），预后较差，因此需要新的治疗方法。在目前的综述中，我们讨论了 BTC 现有治疗方法的局限性、mTOR 信号在 BTC 中的重要性以及 mTOR 抑制剂作为未来 BTC 治疗方法的可能作用。吉西他滨为基础的化疗仍然是 BTC 的标准治疗方法，晚期 BTC 尚无靶向治疗方法。PI3K/AKT/mTOR 信号通路与其他几个通路和网络相连，调节癌症的增殖和进展。新出现的证据表明，mTOR 的激活与 BTC 的肿瘤发生和耐药性有关。雷帕霉素类似物，如依维莫司，部分抑制 mTOR 复合物 1（mTORC1），并在 BTC 的体外和体内显示出抗癌活性。雷帕霉素类似物在临床试验中显示出对晚期 BTC 患者的一些活性。针对 ATP 结合口袋的新一代 mTOR 抑制剂可抑制 TORC1 和 TORC2，并在体外和体内显示出更强的抗肿瘤作用，然而，需要进行前瞻性临床试验来证明其在晚期 BTC 患者中的疗效。
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