Pancreatic cancer(PC) is a devastating disease with a poor prognosis; however, few treatment options are available and the search continues for feasible molecular therapeutic targets, both in the tumor itself and in the tumor microenvironment. The mechanistic target of rapamycin (mTOR) signaling pathway has emerged as an attractive target due to its regulatory role in multiple cellular processes, including metabolism, proliferation, survival, and differentiation, under physiological and pathological conditions. Although mTOR-regulated events in tumor cells and the tumor microenvironment are known to restrict the development and growth of tumor cells, monotherapy with mTOR inhibitors has shown limited efficacy against PC to date, suggesting the need for alternative approaches. In this review, we describe the mechanisms by which mTOR modulates the PC microenvironment and suggest ways its function in immune cells might be exploited for the treatment of PC. We also discuss preclinical and clinical studies with mTOR inhibitors in combination with other therapeutic strategies, most notably immunotherapy. Finally, we highlight the promise that mTOR combinatorial therapy may hold for the treatment of PC in the near future.

中文翻译：

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雷帕霉素在肿瘤微环境中的机制靶标及其作为胰腺癌治疗靶标的潜力。

胰腺癌是一种破坏性疾病，预后差。然而，几乎没有治疗选择，并且在肿瘤本身和肿瘤微环境中都在寻找可行的分子治疗靶标。雷帕霉素（mTOR）信号传导途径的机械靶标已成为一种有吸引力的靶标，原因是它在生理和病理条件下对多种细胞过程的调节作用，包括代谢，增殖，存活和分化。尽管已知肿瘤细胞和肿瘤微环境中mTOR调控的事件会限制肿瘤细胞的发育和生长，但迄今为止，使用mTOR抑制剂进行单药治疗对PC的疗效有限，这表明需要其他方法。在这篇评论中 我们描述了mTOR调节PC微环境的机制，并提出了可能利用其在免疫细胞中的功能来治疗PC的方法。我们还将讨论mTOR抑制剂与其他治疗策略（最著名的是免疫治疗）相结合的临床前和临床研究。最后，我们强调了mTOR联合疗法在不久的将来可用于治疗PC的希望。