: Precise Proteomics Technology for Mapping Receptor Protein Neighborhoods at the Cancer Cell Surface.

Cell surface receptors are pivotal to cancer cell transformation, disease progression, metastasis, early detection, targeted therapy, drug responses, and clinical outcomes. Since they coordinate complex signaling communication networks in the tumor microenvironment, mapping the physical interaction partners of cell surface receptors in vivo is vital for understanding their roles, functional states, and suitability as therapeutic targets. Yet traditional methods like immunoprecipitation and affinity purification-mass spectrometry often fail to detect key but weak or transient receptor-protein interactions. Proximity labeling, a cutting-edge proteomics technology, addresses these technical challenges by enabling precise mapping of protein neighborhoods around a receptor target on the cell surface of cancer cells. This technique has been successfully applied in vitro and in vivo for proteomic mapping across various model systems. This review explores the fundamental principles, technologies, advantages, limitations, and applications of proximity labeling in cancer biology, focusing on mapping receptor microenvironments. By advancing mechanistic insights into cancer cell receptor signaling mechanisms, proximity labeling is poised to transform cancer research, improve targeted therapies, and illuminate avenues to overcome drug resistance.