Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University Munich, 81675, München, Germany.
Department of Hematology, Oncology and Tumor Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
Br J Cancer. 2021 Feb;124(3):531-538. doi: 10.1038/s41416-020-01119-6. Epub 2020 Oct 19.
An urgent medical need to develop novel treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) exists. However, despite various efforts in the histopathological and molecular subtyping of PDAC, novel targeted or specific therapies have not been established. Posttranslational modifications (PTMs) with ubiquitin-like proteins, including small ubiquitin-like modifiers (SUMOs), mediate numerous processes that can contribute to the fitness and survival of cancer cells. The contribution of SUMOylation to transcriptional control, DNA repair pathways, mitotic progression, and oncogenic signalling has been described. Here we review functions of the SUMO pathway in PDAC, with a special focus on its connection to an aggressive subtype of the disease characterised by high MYC activity, and discuss SUMOylation inhibitors under development for precise PDAC therapies.
目前，临床上急需为胰腺导管腺癌（PDAC）患者开发新的治疗策略。然而，尽管在 PDAC 的组织病理学和分子分型方面做出了各种努力，但尚未建立新的靶向或特异性治疗方法。翻译后修饰（PTMs）与泛素样蛋白有关，包括小分子泛素样修饰物（SUMO），介导许多可促进癌细胞适应性和存活的过程。SUMO 化在转录调控、DNA 修复途径、有丝分裂进展和致癌信号转导中的作用已有描述。在这里，我们综述了 SUMO 通路在 PDAC 中的功能，特别关注其与一种侵袭性亚型的关联，这种亚型的特征是 MYC 活性高，并讨论了正在开发用于精确治疗 PDAC 的 SUMO 化抑制剂。
