A Timely Shift from Shotgun to Targeted Proteomics and How It Can Be Groundbreaking for Cancer Research

Abstract

The fact that cancer is a leading cause of death all around the world has naturally sparked major efforts in the pursuit of novel and more efficient biomarkers that could better serve as diagnostic tools, prognostic predictors, or therapeutical targets in the battle against this type of disease. Mass spectrometry-based proteomics has proven itself as a robust and logical alternative to the immuno-based methods that once dominated the field. Nevertheless, intrinsic limitations of classic proteomic approaches such as the natural gap between shotgun discovery-based methods and clinically applicable results have called for the implementation of more direct, hypothesis-based studies such as those made available through targeted approaches, that might be able to streamline biomarker discovery and validation as a means to increase survivability of affected patients. In fact, the paradigm shifting potential of modern targeted proteomics applied to cancer research can be demonstrated by the large number of advancements and increasing examples of new and more useful biomarkers found during the course of this review in different aspects of cancer research. Out of the many studies dedicated to cancer biomarker discovery, we were able to devise some clear trends, such as the fact that breast cancer is the most common type of tumor studied and that most of the research for any given type of cancer is focused on the discovery diagnostic biomarkers, with the exception of those that rely on samples other than plasma and serum, which are generally aimed toward prognostic markers. Interestingly, the most common type of targeted approach is based on stable isotope dilution-selected reaction monitoring protocols for quantification of the target molecules. Overall, this reinforces that notion that targeted proteomics has already started to fulfill its role as a groundbreaking strategy that may enable researchers to catapult the number of viable, effective, and validated biomarkers in cancer clinical practice.

Keywords: biomarkers; cancer; diagnosis; mass spectrometry; targeted proteomics.

Figure 1

Distribution of the number of studies using targeted approaches according to the methods used, further grouped by the use of sample enrichment prior to RP-LC-MS.

Figure 2

Distribution of the number of studies according to the approach given by the authors. (A) Based on the use of targeted proteomics dedicated to different types of cancer, further grouped into the clinical application of each biomarker; (B) the clinical application of different biomarkers found in within the studied cancer types; (C) distribution of the studies using different sample types according to the clinical application of the biomarkers. These charts were based on data from all studies included in this review that focused on the analysis of cancer-related samples, either from human, or from other species or in vitro tests.