Pharmacoproteomic approach to the study of drug mode of action, toxicity, and resistance: applications in diabetes and cancer

Abstract

Proteomics is a powerful technique for investigating protein expression profiles in biological systems and their modifications in response to stimuli or to particular physiological or pathophysiological conditions. It is therefore a technique of choice for the study of drug mode of action, side-effects, toxicity and resistance. It is also a valuable approach for the discovery of new drug targets. All these proteomic applications to pharmacological issues may be called pharmacoproteomics. The pharmacoproteomic approach could be particularly useful for the identification of molecular alterations implicated in type 2 diabetes and for further characterization of existing or new drugs. In oncology, proteomics is widely used for the identification of tumour-specific protein markers, and pharmacoproteomics is used for the evaluation of chemotherapy, particularly for the characterization of drug-resistance mechanisms. The large amount of data generated by pharmacoproteomic screening requires the use of bioinformatic tools to insure a pertinent interpretation. Herein, we review the applications of pharmacoproteomics to the study of type 2 diabetes and to chemoresistance in different types of cancer and the current state of this technology in these pathologies. We also suggest a number of bioinformatic solutions for proteomic data management.

Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes

“…It has proven to be a technique of choice for study of modes of drug action, side-effects, toxicity and resistance, and is also a valuable approach for the discovery of new drug targets. These proteomic applications to pharmacological issues have been dubbed pharmacoproteomics [11]. Currently, many proteomic studies use two-dimensional electrophoresis (2-DE) to separate proteins [12]; we have recently used this proteomic approach to describe the cellular proteome of normal and osteoarthritic human chondrocytes in basal conditions [13,14] and also under IL-1β stimulation [15].…”

Mechanism of Cell Adaptation

“…To overcome the toxic effects of curative compounds, cancer cells have to continuously develop the capability to implement and strengthen normal physiological functions or to mature de novo mechanisms of resistance against single selected compounds or multiple agents, often apparently unrelated. Nearly any type of chemoresistances is a multifactorial process involving induction of drug-detoxifying mechanism, quantitative and qualitative modification of drug targets, arrest of cell cycle, regulation of DNA replication or reparation mechanisms, and modulation of apoptosis 4 (Fig. 1).…”

Precision Dosing: Public Health Need, Proposed Framework, and Anticipated Impact

“…Improved evidence‐based modeling approaches are needed to make genetic information available at the time of prescribing if clinicians are to use these in routine patient care. In addition to genomic biomarkers, the use of transcriptomic, proteomic, and metabolomic methods may also allow for better tailoring of drug treatment …”