Advancements in Single-Cell Proteomics and Mass Spectrometry-Based Techniques for Unmasking Cellular Diversity in Triple Negative Breast Cancer

not-yet-known not-yet-known not-yet-known unknown Triple-negative breast cancer (TNBC) represents a particularly aggressive and complex form of breast cancer lacking targeted treatment options. Its extensive intratumoral heterogeneity drives disease progression and complicates therapeutic responses. The emergence of single-cell proteomics has revolutionized biological research, expanding beyond conventional deep sequencing and imaging techniques. Proteins, as essential cellular components, offer a more direct link to phenotype and cell behavior than other biomolecules, underscoring the importance of advancing single-cell proteomic techniques for deeper insights into fundamental biology and disease mechanisms. In recent years, combining the advancements in sample preparation techniques with the power of mass spectrometry boosted the development of single-cell proteomics research, complementing transcriptomic approaches despite inherent challenges like the inability to amplify proteins akin to transcripts. In this review, we discussed the current advancements in single-cell proteomics, covering workflow, sample preparation techniques, and recent advances in mass spectrometry-based techniques. Toward the end, we explore the challenges and future directions that the scientific community must address to advance this technology. We conclude by urging the rapid resolution of these problems, enabling single-cell proteomics to become part of a robust, high-throughput, and scalable single-cell multi-omics platform that can provide deep biological insights into the diagnosis and treatment of TNBC.