Advances, challenges, and limitations in serum-proteome-based cancer diagnosis

Recent advances in medicine have dramatically reduced the incidence and mortality of many cardiovascular, infectious, and certain neoplastic diseases; the overall mortality for most malignant solid tumors remains high. The poor prognosis in these cancers is due, in part, to the absence of adequate early screening tests, leading to delays in diagnosis. Three strategies have been applied to fight cancer: analysis of the molecular mechanisms involved in its pathogenesis and progression, improvement of early diagnosis, and the development of novel treatment strategies. There have been major advances in our understanding of cancer biology and pathogenesis and in the development of new (targeted) treatment modalities. However, insufficient progress has been made with respect to improving the methods for the early diagnosis and screening of many cancers. Therefore, cancer is often diagnosed at advanced stages, delaying timely treatment and leading to poor prognosis. Proteome analysis has recently been used for the identification of biomarkers or biomarker patterns that may allow for the early diagnosis of cancer. This tool is of special interest, since it allows for the identification of tumor-derived secretory products in serum or other body fluids. In addition, it may be used to detect reduced levels or loss of proteins in the serum of cancer patients that are present in noncancer individuals. These changes in the serum proteome may result from cancer-specific metabolic or immunological alterations, which are, at least partly, independent of tumor size or mass, thereby facilitating early discovery.