Iriana Sentia, Ahmed Shahzad, Gong Jun, Annamalai Alagappan Anand, Tuli Richard, Hendifar Andrew Eugene
Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA , USA.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
Front Oncol. 2016 Apr 25;6:99. doi: 10.3389/fonc.2016.00099. eCollection 2016.
Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future.
晚期胰腺导管腺癌（PDAC）的治疗选择有限；然而，针对特定肿瘤相关分子特征的新疗法可能对某些患者群体有所帮助。新出现的临床前数据表明，在特定KRAS依赖的PDAC亚型中抑制雷帕霉素哺乳动物靶点（mTOR）可在体外和体内抑制肿瘤发生。单药mTOR抑制的早期II期研究未显示出前景。然而，研究表明，沿mTOR信号通路多个步骤的联合抑制可能通过靶向肿瘤耐药机制导致持续反应。在分子定义的PDAC亚群中协同抑制mTOR以及特定KRAS依赖的突变可能为未来的治疗提供一种可行的替代方案。
