Chemical biology has been attracting a lot of attention because of the key roles of chemical methods and techniques in helping to decipher and manipulate biological systems. Although chemical biology encompasses a broad field, this review will focus on chemical biology aimed at using exogenous chemical probes to interrogate, modify and manipulate biological processes, at the cellular and organismal levels, in a highly controlled and dynamic manner. In this area, many advances have been achieved for cancer biology and therapeutics, from target identification and validation based on active anticancer compounds (forward approaches) to discoveries of anticancer molecules based on some important targets including protein-protein interaction (reverse approaches). Herein we attempt to summarize some recent progresses mainly from China through applying chemical biology approaches to explore molecular mechanisms of carcinogenesis. Additionally, we also outline several new strategies for chemistry to probe cellular activities such as proximity-dependent labeling methods for identifying protein-protein interactions, genetically encoded sensors, and light activating or repressing gene expression system.
化学生物学因其在解析和操控生物系统中的关键方法和技术而备受关注。尽管该领域涵盖广泛,本综述将聚焦于运用外源性化学探针,在细胞和生物体层面以高度可控的动态方式探索、修饰及调控生物过程的化学生物学研究。在此领域中,癌症生物学与治疗学已取得诸多进展——从基于活性抗癌化合物的靶点识别与验证(正向策略),到针对蛋白质相互作用等重要靶点发现抗癌分子的研究(反向策略)。本文旨在总结中国学者近期通过化学生物学方法探索癌变分子机制的主要进展,同时概述若干化学探测细胞活性的新策略,包括用于识别蛋白质相互作用的邻近标记技术、基因编码传感器以及光激活或光抑制基因表达系统。
Phenotype and target-based chemical biology investigations in cancers