Proteomic analysis in cancer research: potential application in clinical use

Abstract

The ultimate goal of cancer proteomics is to adapt proteomic technologies for routine use in clinical laboratories for the purpose of diagnostic and prognostic classification of disease states, as well as in evaluating drug toxicity and efficacy. The novel technologies allows researchers to facilitate the comprehensive analyses of genomes, transcriptomes, and proteomes in health and disease. The information that is expected from such technologies may soon exert a dramatic change in cancer research and impact dramatically on the care of cancer patients. Analysis of tumor-specific proteomic profiles may also allow better understanding of tumor development and the identification of novel targets for cancer therapy. The localization of gene products, which is often difficult to deduce from the sequence, can be determined experimentally. Mechanisms, such as regulation of protein function by proteolysis, recycling, and isolation in cell compartments, affect gene products, not genes. Finally, protein-protein interactions and the molecular composition of cellular structures can be determined only at the protein level. The biological variability among patient samples as well as the great dynamic range of biomarker concentrations are currently the main challenges facing efforts to deduce diagnostic patterns that are unique to specific disease states. While several strategies exist to address this problem, we have tried to offer a wide perspective about the current possibilities.

What does it need to be a biomarker? Relationships between resolution, differential quantification and statistical validation of protein surrogate biomarkers

“…Expectations to carry MS results directly to clinical profiling [36,37] seem exaggerated [38][39][40]. The views presented in this article are, therefore, only partially in line (or even completely controversial) with regard to a number of recently published reviews, which offer a variety of essentially MS-based technological approaches for the biomarker problem [6,[41][42][43][44][45]. Supplementary and independent confirmation of molecular information from MS-based proteomic studies, e.g., by antibody-based technologies, appears to be highly desirable [46,47].…”

Important Clues of Current Phosphoproteomic Approaches for Clinical Research

“…Comparative/quantitative analysis of highquality clinical biospecimen (e.g., tissue and biofluids) of human cancer proteome landscape can potentially reveal protein/peptide biomarkers responsible for this disease by means of their altered levels of expression, PTMs as well as diff erent forms of protein variants. Despite technological advances in proteomics, major hurdles still exist at every step of the bio marker development pipeline [52][53][54][55][56][57][58][59][60][61][62][63].…”

The Journey to Regulation of Protein-Based Multiplex Quantitative Assays

“…This vast discrepancy between discovery using proteomic technologies and the number of FDA-approved protein analytes suggests a deficiency in the effective translation of clinical proteomics within the biomarker pipeline. This state of affairs is possibly due to several factors (3)(4)(5)(6) including: (a) technological variation within and across platforms; (b) an inability to credential biomarker candidates before costly and time-consuming clinical-qualification studies that use well-established methodologies; (c) the research community's lack of knowledge about the evaluation criteria required for these distinct processes in the pipeline and about regulatory science; and (d) the failure of biomarkers in clinical qualification. In this report, we provide the research community with a basic resource for defining and explaining the regulatory processes for translating biomarker candidates discovered in research laboratories into multiplex protein-based assays for clinical use.…”