The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors.

中文翻译：

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多西紫杉醇和替西罗莫司治疗难治性实体瘤的 I 期研究。

哺乳动物雷帕霉素靶蛋白 (mTOR) 是磷脂酰肌醇 3-激酶/Akt 信号通路的下游介质，在细胞增殖、生长、分化、迁移和存活中发挥核心作用。Temsirolimus (CCI-779) 是一种选择性 mTOR 抑制剂，是雷帕霉素 (西罗莫司) 的酯类似物，具有改善的水溶性和药代动力学 (PK) 特性。临床前研究已证实紫杉烷类药物和 mTOR 抑制剂的组合对癌细胞系（乳腺癌、前列腺癌）具有累加和协同的抗肿瘤活性。我们进行了一项 I 期开放标签剂量递增研究，以确定多西紫杉醇联合替西罗莫司治疗难治性实体瘤患者的最大耐受剂量 (MTD)。