Innovative and progressive proteomic technologies are needed for large-scale analysis of these broad-range processes. Further, the extensive temporal dynamic range of the proteoforms adds complexity to proteome analysis. Proteoforms can, therefore, act as the ultimate long-range functional effectors of a gene and increase the structural and functional diversity of the proteome. Each proteoform has a specific subcellular location, where it interacts with surrounding molecules and may form a complex to carry out a specific biological function, and consequently have important effects at the system level.
These diverse molecular forms of a protein product of a single gene are termed ‘proteoforms’. This yields a variety of protein products relative to the canonical form. The variations in protein product may result from genetic changes, mutations, transcriptional variations, RNA splicing, translational error, protein folding, proteolytic cleavage of a signal peptide, or a myriad of post-translational modifications (PTMs). In the field of proteomics, there has been a paradigm change from protein expression to proteoform abundance from the genome. Proteomics includes the assessment of global protein abundance, proteoform levels, spatial conformations, chemical modifications, cellular localization, proteoform functions, cofactors, and interacting partner networks. The proteome encompasses the entire set of proteoforms present at a certain time in a cell, tissue, or individual in a given biological setting. Overall, the future of oncoproteomics holds enormous potential for translating technologies from the bench to the bedside. We further provide exemplars from recent oncoproteomics applications in the discovery of biomarkers in various cancers, drug discovery, and clinical treatment. The information gained from such technologies has drastically improved cancer research. This review provides an overview of proteomics technologies that assist the discovery of novel drug targets, biomarkers for early detection, surveillance, prognosis, drug monitoring, and tailoring therapy to the cancer patient.
Investigation of tumor-specific proteomic profiles in conjunction with healthy controls provides crucial information in mechanistic studies on tumorigenesis, metastasis, and drug resistance.
Oncoproteomics studies help to develop and validate proteomics technologies for routine application in clinical laboratories for (1) diagnostic and prognostic categorization of cancer, (2) real-time monitoring of treatment, (3) assessing drug efficacy and toxicity, (4) therapeutic modulations based on the changes with prognosis and drug resistance, and (5) personalized medication. The knowledge of cancer has improved the treatment and clinical management however, the survival rates have not increased significantly, and cancer remains a major cause of mortality. These are modulated by various factors such as molecular, genetic, tissue, cellular, ethnic/racial, socioeconomic status, environmental, and demographic differences that vary with time. Cancer is a complicated and heterogeneous disease, and the onset and progression involve multiple dysregulated proteoforms and their downstream signaling pathways. Proteomics continues to forge significant strides in the discovery of essential biological processes, uncovering valuable information on the identity, global protein abundance, protein modifications, proteoform levels, and signal transduction pathways.
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