Discovery of anti-tumor targets based on photo-affinity labeling

The development and progression of tumors are closely related to functional abnormalities of specific proteins. Therefore, discovering and identifying these key protein targets is central to the research and development of innovative anti-tumor drugs. Photo-affinity Labeling (PAL) technology, as a powerful chemical proteomics tool, enables the incorporation of photoreactive groups into small molecule probes. Under specific wavelengths of light, these probes form irreversible covalent linkages with neighboring target proteins, thereby "capturing" and labeling transient molecular interactions. This technique offers unique advantages such as high specificity and high throughput. This review systematically elaborates on the fundamental principles of PAL technology, the design strategies of its key components, and its experimental workflow. We focus on summarizing the recent advancements of PAL technology in discovering novel anti-tumor targets, including the direct identification of intracellular anti-cancer targets of small molecule inhibitors and the revelation of unknown targets of natural products in tumor cells. Furthermore, we discuss future directions, such as integrating PAL with bioinformatics analysis and multi-omics approaches to identify anti-tumor targets. In summary, PAL technology provides an irreplaceable technical means for the precise and efficient discovery of anti-tumor drug targets, significantly advancing the fields of precision oncology and innovative drug development.