液-液相分离（LLPS）是多种生物过程（包括癌发生和癌症进展）普遍存在的框架。虽然从 LLPS 的角度靶向癌症提供了一个机会，可以对具有癌症驱动潜力的传统非成药药物进行药物治疗，但癌症相关 LLPS (CAL) 蛋白的治疗价值仍然难以捉摸。在这里，我们基于泛癌中蛋白质编码相关突变和转录丰度报告了 CAL 蛋白质编码基因特征的基因组图谱、预后相关性、免疫浸润关联、下游途径改变和小分子反应性。在一系列癌症中观察到 CAL 蛋白编码相关突变和转录丰度与总生存期和无进展生存期的相关性，并通过内在紊乱区域 (IDR) 富集和非 IDR 富集突变的患者之间的生存结果差异进行进一步表征。子宫内膜癌。由于 CAL 蛋白编码相关基因组突变，信号通路和免疫浸润的普遍模式发生了改变，涉及各种癌症类型中肿瘤发生的关键组成部分以及包括 MAPK 信号通路在内的既定治疗靶点，并暗示可能具有高度反应性的炎症肿瘤免疫到免疫治疗。 LLPS 抑制剂增强了顺铂/紫杉醇在选择性癌细胞系中的细胞毒性。这些发现为通过 LLPS 调节协同作用进行合理的化疗、靶向和免疫治疗创新提供了初步证据。版权所有：© 2023 Sun 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Liquid-liquid phase separation (LLPS) is characterized as an ubiquitous framework for diverse biological processes including carcinogenesis and cancer progression. While targeting cancer from perspective of LLPS offers an opportunity to drug the conventionally undruggables with cancer-driving potential, the therapeutic value of cancer associated LLPS (CAL) proteins remains elusive. Here, we report the genomic landscape, prognostic relevance, immune-infiltration association, down-stream pathway alteration and small molecular responsiveness of CAL protein-coding gene signatures based on protein-coding associated mutations and transcriptional abundance in pan-cancer. Correlations of CAL protein-coding associated mutations and transcriptional abundances to overall survival and progression-free survival were observed in an array of cancers and further characterized by differential survival outcomes between patients with intrinsic disordered region (IDR) enriched and non-IDR enriched mutations in endometrial cancer. Altered signaling pathways and universal pattern of immune infiltrates on account of CAL protein-coding associated gene-set mutations involved key components of oncogenesis in various cancer types and well established therapeutic targets including MAPK signaling pathway and implied an inflamed tumor immunity that might be highly responsive to immunotherapy. LLPS inhibitor enhanced cytotoxicity of cisplatin/paclitaxel in selective cancer cell lines. These findings provide preliminary evidences for rational chemo-, targeted- and immuno-therapeutic innovation with LLPS regulating synergy.Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.