美国贝勒医学院章冰等研究人员合作发现，泛癌症蛋白质组学扩展治疗靶点的范围。这一研究成果于2024年6月24日在线发表在国际学术期刊《细胞》上。
研究人员整合了临床肿瘤蛋白质组学分析联盟（CPTAC）10种癌症类型1043名患者的蛋白质组学数据和其他公共数据集，以确定潜在的治疗靶点。对2863种可成药蛋白质的泛癌症分析显示了广泛的丰度范围，并确定了影响mRNA蛋白相关性的生物因素。
整合肿瘤的蛋白质组数据和细胞系的基因筛选数据，确定蛋白质过表达或过度激活驱动的可成药依赖性，从而准确预测有效的药物靶点。
蛋白质基因组鉴定合成致死率为靶向肿瘤抑制基因缺失提供了一种策略。将蛋白质基因组分析与MHC结合预测相结合，可将突变KRAS肽优先列为有前景的公共新抗原。
通过计算识别共同的肿瘤相关抗原并进行实验确认，可将多肽提名为免疫疗法靶点。这些分析结果汇总在https://targets.linkedomics.org网站上，形成了用于辅助诊断、药物再利用和治疗开发的蛋白质和多肽靶点的综合图谱。
研究人员表示，美国食品和药物管理局（FDA）批准的抗癌药物所针对的蛋白质不到200种。
附：英文原文
Title: Pan-cancer proteogenomics expands the landscape of therapeutic targets
Author: Sara R. Savage, Xinpei Yi, Jonathan T. Lei, Bo Wen, Hongwei Zhao, Yuxing Liao, Eric J. Jaehnig, Lauren K. Somes, Paul W. Shafer, Tobie D. Lee, Zile Fu, Yongchao Dou, Zhiao Shi, Daming Gao, Valentina Hoyos, Qiang Gao, Bing Zhang
Issue&Volume: 2024-06-24
Abstract: Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org, form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development.
DOI: 10.1016/j.cell.2024.05.039
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00583-X