The unsuccessful hunt for pancreatic cancer biomarkers – time to Search deeper in the proteome

Proteomics has been successful in the identification of reliable diagnostic and prognostic biomarkers for a wide variety of malignancies. In addition, therapeutic biomarkers have allowed for the identification of radio- or chemo-resistant phenotypes and the selection of sub-type-specific therapies. However, the hunt for biomarkers of any kind related to pancreatic cancer has so far turned up unfruitful. The few high-potential candidates which have been found so far, still do not show the desired sensitivity and specificity. In this light, it is hence better to rely on a combination of proteins in the form of a biomarker panel, which attempts to cover the entire spectrum of the disease state. The observed heterogeneity and the presence of cancer stem cells in different pancreatic cancers are important issues that need to be tackled efficiently in the search for significant biomarkers. With the next-generation of mass spectrometers combining quadrupole, orbitrap, and ion trap mass analysis systems it is now time to go beyond the search for biomarkers at a whole protein level and start looking at post-translational modifications (PTMs) such a phosphorylation, ubiquitination, acetylation and methylation for subtle changes which are known to have a dramatic effect on protein activation, function or half-life. This makes PTMs a key focus for future investigations in this area of research.