Application of Advanced Mass Spectrometry-Based Proteomics to Study Hypoxia Driven Cancer Progression

Abstract

Cancer is one of the largest contributors to the burden of chronic disease in the world and is the second leading cause of death globally. It is associated with episodes of low-oxygen stress (hypoxia or ischemia/reperfusion) that promotes cancer progression and therapeutic resistance. Efforts have been made in the past using traditional proteomic approaches to decipher oxygen deprivation stress-related mechanisms of the disease initiation and progression and to identify key proteins as a therapeutic target for the treatment and prevention. Despite the potential benefits of proteomic in translational research for the discovery of new drugs, the therapeutic outcome with this approach has not met expectations in clinical trials. This is mainly due to the disease complexity which possess a multifaceted molecular pathology. Therefore, novel strategies to identify and characterize clinically important sets of modulators and molecular events for multi-target drug discovery are needed. Here, we review important past and current studies on proteomics in cancer with an emphasis on recent pioneered labeling approaches in mass spectrometry (MS)-based systematic quantitative analysis to improve clinical success. We also discuss the results of the selected innovative publications that integrate advanced proteomic technologies (e.g. MALDI-MSI, pSILAC/SILAC/iTRAQ/TMT-LC-MS/MS, MRM-MS) for comprehensive analysis of proteome dynamics in different biosystems, including cell type, cell species, and subcellular proteome (i.e. secretome and chromatome). Finally, we discuss the future direction and challenges in the application of these technological advancements in mass spectrometry within the context of cancer and hypoxia.

Application of Mass Spectrometry in Pancreatic Cancer Translational Research

“…Among the strategies for analyzing the proteome’s expression, structure, and function, LC-MS has played and will continue to take a vital role ( 19 ). On the one hand, high-throughput proteomics based on LC-MS has been widely used to discover tumor biomarkers.…”

Quantitative proteomics characterization of cancer biomarkers and treatment

“…Quantitative proteomics is a promising tool for revealing the molecular mechanisms of drug action. 58 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 Proteomics drug maps have greatly promoted the discovery of drug targets. After the quantitative analysis for 10,000 proteins and 55,000 phosphorylation sites (p-sites) from 125 cancer cell lines, the proteome activity landscapes were obtained.…”

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence

“…During the last decade, high-throughput proteomics coupled with mass spectrometry (MS) and integrated with advanced platforms (e.g., array- or three-dimensional liquid chromatography-based, microfluidic) have offered powerful tools to finely characterize proteins in biological systems [ 39 , 40 , 41 , 42 , 43 ]. Proteomics and subproteomics methods have brought new insights to the discovery of biomarkers commonly present at low concentration levels that can be associated with disease progression [ 44 , 45 ].…”