Chemical proteomics studies the effects of drugs upon a cellular proteome. Due to the complexity and diversity of tumors, the response of cancer cells to drugs is also heterogeneous, and thus, proteome analysis at the single-cell level is needed. Here, we demonstrate that single-cell proteomics techniques have become quantitative enough to tackle the drug effects on target proteins, enabling single-cell chemical proteomics (SCCP). Using SCCP, we studied here the time-resolved response of individual adenocarcinoma A549 cells to anticancer drugs methotrexate, camptothecin, and tomudex, revealing the early emergence of cellular subpopulations committed and uncommitted to death. As a novel and useful approach to exploring the heterogeneous response to drugs of cancer cells, SCCP may prove to be a breakthrough application for single-cell proteomics.

中文翻译：

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单细胞化学蛋白质组学 (SCCP) 探讨癌细胞死亡的时间和异质性


化学蛋白质组学研究药物对细胞蛋白质组的影响。由于肿瘤的复杂性和多样性，癌细胞对药物的反应也具有异质性，因此需要单细胞水平的蛋白质组分析。在这里，我们证明单细胞蛋白质组学技术已经足够定量，可以解决药物对靶蛋白的影响，从而实现单细胞化学蛋白质组学（SCCP）。我们使用 SCCP 研究了单个腺癌 A549 细胞对抗癌药物甲氨蝶呤、喜树碱和 tomudex 的时间分辨反应，揭示了致死和未致死细胞亚群的早期出现。作为探索癌细胞对药物异质反应的一种新颖且有用的方法，SCCP 可能被证明是单细胞蛋白质组学的突破性应用。