Mass spectrometry-based analyses of the low-molecular-weight fraction of serum proteome allow identifying proteome profiles (signatures) that are potentially useful in detection and classification of cancer. Several published studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. However due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by MALDI/SELDI-ToF spectrometry has been approved for routine diagnostics. Noteworthy, several components of proposed cancer signatures, especially those characteristic for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response. This indicated that among cancer biomarker candidates to be possibly identified by serum proteome profiling were rather those reflecting overall influence of a disease (and the therapy) upon the human organism, than products of cancer-specific genes. Current paper focuses on changes in serum proteome that are related to response of patient’s organism to progressing malignancy and toxicity of anticancer treatment. In addition, several methodological issues that affect robustness and interlaboratory reproducibility of MS-based serum proteome profiling are discussed. 1. Cancer Markers and Clinical Proteomics Biological factors (e.g., proteins), whose status and/or quantity reflect the risk of a disease, severity of an illness, or the effects of therapy are called markers or biomarkers. In oncology, appropriately selected sets of markers can provide information about carcinogenic triggers to which the organism was exposed, detect early changes (hyperplasia, dysplasia) that appear prior to the occurrence of overt forms of cancer, as well as monitor efficacy and toxicity of the treatment. Such factors (i.e., potential biomarkers) are present in tumor tissues or body fluids, and encompass a wide variety of molecules, including transcription factors, cell-surface receptors, and secreted proteins. Several protein tumor markers have been used for decades in the traditional oncology for detection of cancer, for example, prostate cancer antigen (PSA) or cancer antigen 125?kD (CA125). In fact, effective tumor markers are in great demand since they have the potential to reduce cancer mortality rates by facilitating diagnosis of cancers at early stages and helping to plan tailored treatment. Cancer biomarkers can be divided into prognostic and
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