Chemically Synthesized Fluorescence‐Based Kinase Sensing Systems for Signaling in Cancer

Kinases are an essential class of enzymes that regulate cellular processes through phosphorylation, influencing signal transduction, cell cycle progression, and apoptosis. Dysregulation of kinase activity is a hallmark of cancer, contributing to tumorigenesis, metastasis, and therapeutic resistance. Therefore, precise detection and monitoring of kinase activity are essential for understanding cancer biology and advancing diagnostics and therapeutics. Among various detection methods, fluorescence‐based kinase sensing systems have emerged as highly sensitive, real‐time tools for investigating kinase function. These systems leverage fluorescent moieties, either genetically encoded or chemically synthesized, to provide spatial and temporal insights into kinase activity in complex biological environments. This review focuses on chemically synthesized fluorescence‐based kinase sensing systems, which offer unique advantages, including precise control over concentrations and compatibility with in vitro and in vivo applications. We have classified the chemically synthesized sensing systems into three categories: specific peptide substrate‐based, adenosine triphosphate/adenosine diphosphate‐recognition‐based, and inhibitor‐based sensing systems, each tailored to specific kinase activities. Compared to genetically encoded systems, chemically synthesized sensors demonstrate greater versatility and are better suited for quantitative high‐throughput applications. This review explores the design, mechanisms, and applications of these systems in cancer biology, highlighting their potential for identifying kinase biomarkers, optimizing targeted therapies, and advancing personalized medicine.