mTOR抑制剂在激素受体阳性乳腺癌治疗中的研究进展.pdfVIP

1408 中国肿瘤临床2013年第40卷第22期 Chin J Clin Oncol 2013,Vol.40,No.22 · · 综 述 mTOR抑制剂在激素受体阳性乳腺癌治疗中的研究进展 贾晓青 综述 柳光宇 审校 摘要 靶向激素受体（hormonereceptor，HR）和人类表皮生长因子（humanepidermalgrowthfactorreceptor2，HER-2）对激素 受体阳性乳腺癌的治疗至关重要，然而原发或继发内分泌治疗耐药及后续的疾病进展仍不可避免。人哺乳动物雷帕霉素位点 （mammaliantargetofrapamycin，mTOR）是细胞生长和分化的关键调节因子，参与细胞不可控性生长。目前许多研究表明mTOR 通路的激活可能与乳腺癌内分泌治疗耐药相关，阻断此通路有助于消除耐药，维持药物的敏感性。许多靶向mTOR通路的药物 均表现出强大的抗肿瘤效应，在乳腺癌治疗中具有良好前景，且已有许多临床试验结果表明mTOR抑制剂联合内分泌治疗可显 著提高患者的生存率。本文对mTOR信号通路及其抑制剂在内分泌治疗耐药的乳腺癌中的新进展进行综述。 关键词 乳腺癌 内分泌耐药 依维莫司 mTOR抑制剂 坦罗莫司 doi:10.3969/j.issn.1000-8179 Advancements in mTOR inhibitors for the management of hormone receptor-positive breast cancer Xiaoqing JIA, Guangyu LIU Correspondence to: Guangyu LIU; E-mail: liugy123@ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai School of Medicine, Shanghai 200032, China Abstract Therapies targeting endocrine receptors and human epidermal growth factor receptor 2 have become important treat- ment modes for patients with hormone receptor breast cancer. Despite the availability of these options, however, development of prima- ry or secondary drug resistance and subsequent disease progression in patients with advanced disease continue to occur. Mammalian tar- get of rapamycin (mTOR), a key regulator of cell growth and proliferation, has been implicated in the induction of cellular processes leading to the uncontrolled growth of cancer cells. Recent studies have suggested that overactivation of the mTOR pathway may be in- volved in the development of endocrine resistance. Interrupting this signaling cascade may alleviate such resistance and help restore drug sensitivity. A number of agents targeting the mTOR pathway have shown potent anti-tumorigenic effects in vitro, and several