Data independent acquisition mass spectrometry (DIA-MS) in cancer studies: A concise review

Abstract

Advances in proteomics are reshaping our understanding of cancer biology by enabling the direct quantification of proteins and their modifications in complex biological systems. Among emerging mass spectrometry techniques, Data-Independent Acquisition (DIA) has established itself as a transformative approach for cancer proteomics. DIA offers unprecedented depth, reproducibility, and scalability by systematically fragmenting all precursor ions across defined mass ranges, allowing comprehensive proteome coverage and retrospective data analysis. This review highlights the fundamental principles of DIA-MS, recent technological developments—including spectral library-free workflows, and their impact on cancer research. We discuss the application of DIA in tumor classification, biomarker discovery, therapeutic target identification, and treatment response monitoring. Particular attention is given to its compatibility with clinical samples such as formalin-fixed paraffin-embedded (FFPE) tissues and its integration into large-scale efforts like CPTAC. Current challenges with the technique will be explored, including data analysis complexity and standardization, and future directions that could bring DIA-MS closer to clinical utility. DIA-MS is rapidly evolving into a cornerstone technology for precision oncology, with the potential to bridge research and clinical practice through robust, high-resolution proteomic profiling.