Understanding the mechanisms underpinning therapeutic vulnerability of SWI/SNF deficient cancers

了解 SWI/SNF 缺陷癌症治疗脆弱性的机制

• 批准号: 2893209
• 金额: --
• 依托单位: Institute of Cancer Research
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2893209
• 关键词: Understanding; mechanisms; underpinning; therapeutic; vulnerability

SWI/SNF chromatin remodelling complexes regulate gene expression, DNA repair, replication stress responses and chromosome segregation. SWI/SNF genes are mutated in a striking number of cancers, which provides therapeutic opportunities. By identifying synthetic lethal relationships, or genes required for viability in SWI/SNF deficient cells, we can selectively target the cancer. Inhibitors targeting several known synthetic lethal relationships are in clinical use. However, responses are variable, and it is not clear why some SWI/SNF deficient cells are vulnerable, yet others are not. In this project, we will mechanistically explore these vulnerabilities to understand the contexts in which inhibitors are most effective.

SWI/SNF 染色质重塑复合物调节基因表达、DNA 修复、复制应激反应和染色体分离。 SWI/SNF 基因在大量癌症中发生突变，这提供了治疗机会。通过识别合成致死关系或 SWI/SNF 缺陷细胞生存所需的基因，我们可以选择性地靶向癌症。针对几种已知的合成致死关系的抑制剂已在临床使用。然而，反应是可变的，目前还不清楚为什么一些 SWI/SNF 缺陷细胞很脆弱，而另一些则不然。在这个项目中，我们将机械地探索这些漏洞，以了解抑制剂最有效的环境。