Integrating phosphoproteomics into kinase-targeted cancer therapies in precision medicine

Publication date: Available online 3 April 2018
Source:Journal of Proteomics
Author(s): Xiaomo Wu, Xiaohua Xing, Djameel Dowlut, Yongyi Zeng, Jingfeng Liu, Xiaolong Liu
Protein phosphorylation is a post-translational modification that is involved in the regulation of all major biological processes in cells. As a rapid and reversible means to modulate protein activity and transduce signals, aberrant protein phosphorylation is implicated in the onset and progression of most cancer types. Therefore, pharmacological inhibitors against protein kinases are highly pursued therapeutic approaches for treating cancer. Phosphoproteomics has become an important approach for investigating protein phosphorylation, and it is a technique that provides measurements of kinase pathway activation and the circuitry of signalling networks with both spatial and temporal resolution. Combined with the recent advances in mass spectrometry and development in biochemical procedures for phosphopeptide enrichment and computational approaches, high-throughput phosphoproteomics enables the investigation of kinase signalling networks with unprecedented depth. Here, we review the recent progresses in phosphoproteomics methodology and how phosphoproteomics profiling could be implemented in translational research to aid cancer therapies, facilitate novel drug target discovery and overcome the therapeutic obstacles caused by drug resistance.SignificanceIn this review, we summarized the recent progress in mass spectrometry-based phosphoproteomics and discussed how phosphoproteomics profiling can be implemented in translational research to aid cancer therapies, facilitate novel drug target discovery and overcome the therapeutic obstacles caused by drug resistance due to the rapid remodelling of signalling networks in response to kinase inhibitor treatment. In addition, we addressed the insights and challenges of applying MS phosphoproteomics in clinical routine practice in precision medicine. This review will help readers become more familiar with the recent advancements and applications of phosphoproteomics, especially in the field of kinase-targeted cancer therapy.

Graphical abstract

https://ift.tt/2GAkp91