Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-sayama City, Japan.
Cancer Sci. 2021 Feb;112(2):490-497. doi: 10.1111/cas.14768. Epub 2020 Dec 28.
ATP-dependent chromatin remodeling complexes are a group of epigenetic regulators that can alter the assembly of nucleosomes and regulate the accessibility of transcription factors to DNA in order to modulate gene expression. One of these complexes, the SWI/SNF chromatin remodeling complex is mutated in more than 20% of human cancers. We have investigated the roles of the SWI/SNF complex in pancreatic ductal adenocarcinoma (PDA), which is the most lethal type of cancer. Here, we reviewed the recent literature regarding the role of the SWI/SNF complex in pancreatic tumorigenesis and current knowledge about therapeutic strategies targeting the SWI/SNF complex in PDA. The subunits of the SWI/SNF complex are mutated in 14% of human PDA. Recent studies have shown that they have context-dependent oncogenic or tumor-suppressive roles in pancreatic carcinogenesis. To target its tumor-suppressive properties, synthetic lethal strategies have recently been developed. In addition, their oncogenic properties could be novel therapeutic targets. The SWI/SNF subunits are potential therapeutic targets for PDA, and further understanding of the precise role of the SWI/SNF complex subunits in PDA is required for further development of novel strategies targeting SWI/SNF subunits against PDA.
ATP 依赖的染色质重塑复合物是一组表观遗传调节剂，能够改变核小体的组装，并调节转录因子与 DNA 的可及性，从而调节基因表达。这些复合物之一，SWI/SNF 染色质重塑复合物在超过 20%的人类癌症中发生突变。我们研究了 SWI/SNF 复合物在胰腺导管腺癌 (PDA) 中的作用，这是最致命的癌症类型。在这里，我们回顾了关于 SWI/SNF 复合物在胰腺肿瘤发生中的作用的最新文献，以及针对 PDA 中 SWI/SNF 复合物的治疗策略的现有知识。SWI/SNF 复合物的亚基在 14%的人类 PDA 中发生突变。最近的研究表明，它们在胰腺发生癌变中具有上下文相关的致癌或肿瘤抑制作用。为了靶向其肿瘤抑制特性，最近开发了合成致死策略。此外，它们的致癌特性可能是新的治疗靶点。SWI/SNF 亚基是 PDA 的潜在治疗靶点，为了进一步开发针对 PDA 的 SWI/SNF 亚基的新型策略，需要进一步了解 SWI/SNF 复合物亚基在 PDA 中的精确作用。
