Towards defining biomarkers indicating resistances to targeted therapies

An impressive, but often short objective response was obtained in many tumor patients treated with different targeted therapies, but most of the patients develop resistances against these drugs. So far, a number of distinct mechanisms leading to intrinsic as well as acquired resistances have been identified in tumors of distinct origin. These can arise from genetic alterations, like mutations, truncations, and amplifications or due to deregulated expression of various proteins and signal transduction pathways, but also from cellular heterogeneity within tumors after an initial response. Therefore, biomarkers are urgently needed for cancer prognosis and personalized cancer medicine. The application of “ome”-based technologies including cancer (epi)genomics, next generation sequencing, cDNA microarrays and proteomics might led to the predictive or prognostic stratification of patients to categorize resistance mechanisms and to postulate combinations of treatment strategies. This review discusses the implementation of proteome-based analysis to identify markers of pathway (in)activation in tumors and the resistance mechanisms, which represent major clinical problems as a tool to optimize individually tailored therapies based on targeted drugs. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.