Molecular profiling of cancer and drug-induced toxicity using new proteomic technologies

Background: Completion of the mapping of the human genome has brought the field of research in biological sciences into a new dawn of discovery. Within this postgenomics era in science, proteomic technologies are positioned to play a major role in discovery of new biomarkers for early detection of diseases and drug-induced toxicity, new molecular targets for therapy, and new end points for therapeutic efficacy and toxicity. Objective: Development of patient-specific targeted therapeutics with reduced toxicity and increased efficacy using cells or sera from patients with disease. Methods: New proteomic technologies such as laser capture microscopy are providing rapid, easy access to the purified, diseased human cells from tissue specimens that previously has not been possible. Due to limited availability of patient material, highly sensitive mass spectrometric techniques such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) are used to complement 2-dimensional gel electrophoresis for multiparametric protein characterization. Results: The use of high-throughput SELDI-TOF protein pattern generation techniques should prove valuable for new molecular classification of human tumors, disease stages, and drug-induced toxicity. The use of newly developed high-density protein arrays, antibody arrays, and small molecular arrays in conjunction with laser capture microscopy could have a substantial impact on proteomic profiling of human tumors and human tissues affected in response to drug treatments. SELDI-TOF and laser capture microscopy technologies in conjunction with new bioinformatic software will be powerful tools in the near future for identifying protein fingerprints in cells or sera of patients to predict the outcomes of therapies for any diagnosed disease. Conclusions: The application of all new proteomic technologies should enhance our efforts in designing rational drug therapy strategies that are based on an individual patient's molecular profiling of cellular proteins in the disease state and can identify proteomic fingerprints associated with drug-induced toxicity directly in sera samples. This should provide us with the detailed knowledge necessary to develop novel therapeutics for the treatment of diseases and/or detection of diseases and toxicity at an early stage.