Application of Fluorescence- and Bioluminescence-Based Biosensors in Cancer Drug Discovery.

Recent advances in drug discovery have established biosensors as indispensable tools, particularly valued for their precision, sensitivity, and real-time monitoring capabilities. The review begins with a brief overview of cancer drug discovery, underscoring the pivotal role of biosensors in advancing cancer research. Various types of biosensors employed in cancer drug discovery are then explored, with particular emphasis on fluorescence- and bioluminescence-based technologies such as FRET, TR-FRET, BRET, NanoBRET, and NanoBiT. These biosensors have enabled breakthrough discoveries, including the identification of Celastrol as a novel YAP-TEAD inhibitor through NanoBiT-based screening, and the development of TR-FRET assays that successfully identified Ro-31-8220 as a SMAD4R361H/SMAD3 interaction inducer. The integration of biosensors in high throughput screening and validation for cancer drug compounds is examined, highlighting successful applications such as the development of LATS biosensors that revealed VEGFR as an upstream regulator of the Hippo signaling pathway. Real-time monitoring of cellular responses through biosensors has yielded invaluable insights into cancer cell signaling pathways, as demonstrated by NanoBRET assays detecting RAF dimerization and HiBiT systems monitoring protein degradation dynamics. The review addresses challenges linked to biosensor applications, such as maintaining stability in complex tumor microenvironments and achieving consistent sensitivity in HTS applications. Emerging trends are discussed, including integrating artificial intelligence and advanced nanomaterials for enhanced biosensor performance. In conclusion, this review offers a comprehensive analysis of fluorescence- and bioluminescence-based biosensor applications in the dynamic cancer drug discovery field, presenting quantitative evidence of their impact and highlighting their potential to revolutionize targeted cancer treatments.