Alvarez Marcus A, Freitas Júlia Pedó, Mazher Hussain S, Glazer Evan S
Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38163, USA.
J Gastrointest Cancer. 2019 Jun;50(2):207-213. doi: 10.1007/s12029-018-00195-5.
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC.
The literature was searched for peer reviewed manuscripts regarding the use of TGF-β inhibitors in PDAC therapy and the mechanism in which TGF-β intracellular signaling effects patient survival.
TGF-β plays a vital, context-dependent role as both a tumor suppressor and promoter of PDAC. The downstream effects of this duality play a significant role in the immunologic response of the tumor microenvironment (TME), epithelial-mesenchymal transformation (EMT), and the development of metastatic disease. Immunologic pathways have been shown to be successful targets in the treatment of other diseases, though they have not been shown efficacious in PDAC. TGF-β-mediated EMT does play a critical role in PDAC progression in the development of metastases. The use of anti-TGF-β-based therapies in phase I and II clinical trials for metastatic PDAC demonstrate the importance of understanding the role of TGF-β in PDAC progression.
This review clarifies the recent literature investigating the role of anti-TGF-β-based therapy in PDAC and areas ripe for targeted investigations and therapies.
胰腺导管腺癌（PDAC）是美国癌症相关死亡的第四大主要原因，且该疾病的总体发病率正在上升，预计在未来十年将成为癌症相关死亡的第三大主要原因。在过去十年中，治疗方面的微小改善并未改变PDAC患者的总体死亡率。本综述的目的是确定关于基于转化生长因子β（TGF-β）的治疗方法在PDAC患者中作用的新数据。
检索文献，查找关于TGF-β抑制剂在PDAC治疗中的应用以及TGF-β细胞内信号传导影响患者生存的机制的同行评审手稿。
TGF-β作为PDAC的肿瘤抑制因子和促进因子发挥着至关重要的、依赖于背景的作用。这种双重性的下游效应在肿瘤微环境（TME）的免疫反应、上皮-间质转化（EMT）和转移性疾病的发展中起着重要作用。免疫途径已被证明是治疗其他疾病的成功靶点，尽管它们在PDAC中尚未显示出有效性。TGF-β介导的EMT在PDAC转移发展过程中确实起着关键作用。在转移性PDAC的I期和II期临床试验中使用基于抗TGF-β的疗法证明了了解TGF-β在PDAC进展中作用的重要性。
本综述阐明了最近关于基于抗TGF-β疗法在PDAC中的作用以及适合进行靶向研究和治疗的领域的文献。
