Kota Janaiah, Hancock Julie, Kwon Jason, Korc Murray
Department of Medical and Molecular Genetics, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA; The Melvin and Bren Simon Cancer Center, IUSM, Indianapolis, IN, USA; Center for Pancreatic Cancer Research, Indiana University and Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA.
Department of Medical and Molecular Genetics, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA.
Cancer Lett. 2017 Apr 10;391:38-49. doi: 10.1016/j.canlet.2016.12.035. Epub 2017 Jan 14.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies with a 5-year survival rate of 8%. Dense, fibrotic stroma associated with pancreatic tumors is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Targeting stroma is considered as a potential therapeutic strategy to improve anti-cancer drug efficacy and patient survival. Although numerous stromal depletion therapies have reached the clinic, they add little to overall survival and are often associated with toxicity. Furthermore, increasing evidence suggests the anti-tumor properties of stroma. Its complete ablation enhanced tumor progression and reduced survival. Consequently, efforts are now focused on developing stromal-targeted therapies that normalize the reactive stroma and avoid the extremes: stromal abundance vs. complete depletion. In this review, we summarized the state of current and emerging anti-stromal targeted therapies, with major emphasis on the role of miRNAs in PDAC stroma and their potential use as novel therapeutic agents to modulate PDAC tumor-stromal interactions.
胰腺导管腺癌（PDAC）是最致命的人类恶性肿瘤之一，5年生存率为8%。与胰腺肿瘤相关的致密、纤维化基质是药物输送至肿瘤床的主要障碍，并在胰腺癌进展中起关键作用。靶向基质被认为是提高抗癌药物疗效和患者生存率的一种潜在治疗策略。尽管众多基质清除疗法已进入临床，但它们对总生存期的改善甚微，且常伴有毒性。此外，越来越多的证据表明基质具有抗肿瘤特性。其完全消融会促进肿瘤进展并缩短生存期。因此，目前的努力集中在开发使反应性基质正常化并避免走向极端（基质丰富与完全清除）的基质靶向疗法。在本综述中，我们总结了当前及新兴的抗基质靶向疗法的现状，主要侧重于miRNA在PDAC基质中的作用及其作为调节PDAC肿瘤-基质相互作用的新型治疗剂的潜在用途。
