Proteomics and its application to discover chemoresistant biomarkers in human cancer

Abstract

Primary or acquired resistance to traditional cytotoxic chemotherapy remains a major obstacle to the successful management of patients in clinical oncology. The discovery of reliable predictive biomarkers of response to chemotherapy-based treatments, which would lead to individualized therapeutic strategies, is a major challenge in cancer biomarker research. Recent innovative high-throughput proteomic technologies appear as powerful tools for the discovery of novel biomarkers associated with chemotherapy resistance because they facilitate the simultaneous analysis of whole proteomes. The current review describes the plethora of existing mass spectrometry (MS)-based proteomic studies that have been conducted to investigate chemoresistance in human cancer, and emphasize putative biomarkers and protein expression profiles that may be useful in the prediction of clinical response to anticancer therapy. We focus on five fatal cancers (breast, prostate, ovarian, lung and esophageal) and for each cancer type the proteomic approaches utilized for the identification of the novel biomarkers are described. A short overview of both gel-based and gel-free mass spectrometry methods is presented along with a brief summary of the most current methods utilized for validation of putative biomarkers. Although the majority of the putative biomarkers presented in this review are very promising, they have been limited to the discovery stage and they still have to be further clinically validated. Follow-up research should focus on the design of careful prospective multicentre screening studies and large clinical trials in order to identify the biomarkers that work and bring them into clinical practice as soon as possible.