Protein Analytical Assays for Diagnosing, Monitoring, and Choosing Treatment for Cancer Patients

Abstract

Cancer treatment is often hindered by inadequate methods for diagnosing the disease or insufficient predictive capacity regarding therapeutic efficacy. Targeted cancer treatments, including Bcr-Abl and EGFR kinase inhibitors, have increased survival for some cancer patients but are ineffective in other patients. In addition, many patients who initially respond to targeted inhibitor therapy develop resistance during the course of treatment. Molecular analysis of cancer cells has emerged as a means to tailor treatment to particular patients. While DNA analysis can provide important diagnostic information, protein analysis is particularly valuable because proteins are more direct mediators of normal and diseased cellular processes. In this review article, we discuss current and emerging protein assays for improving cancer treatment, including trends toward assay miniaturization and measurement of protein activity.

Detecting post-translational modification signatures as potential biomarkers in clinical mass spectrometry

“…For precision medicine, PTM signatures may either be identified in disease models and then validated in clinical samples or directly identified using clinical samples. Although, for example, specific changes in phosphorylation and glycosylation are increasingly reported as potential markers of disease, and many PTM assays have been developed so far (for instance reviewed in [23][24][25]), only few are really routinely used for diagnostic purposes to date, due to a variety of reasons [26]. We are still in the early days of PTM-specific research and detection and many potential PTM biomarkers and the corresponding assays still need to be validated extensively.…”

How iMALDI can improve clinical diagnostics

“…12 Additionally, sample fixation has the potential to induce artificial patterns particularly for signalling PTMs such as protein phosphorylation, or, conversely, may fail to preserve these. In IHC, results are often interpreted in a semi-quantitative manner, and are manually ranked based on staining intensity which introduces subjectivity and variability into the assays, 13 with a continuing need for improved standardization. 14,15 Recently, Morales-Betanzos et al demonstrated that IHC methods for detecting programmed death-ligand 1 (PD-L1), an important companion diagnostics for immune checkpoint therapies, can suffer severely from interference by endogenous PD-L1 glycosylation patterns that prevent proper epitope recognition, leading to underestimation of PD-L1 expression levels.…”

Label‐Free Direct Electrical Detection of a Histidine‐Rich Protein with Sub‐Femtomolar Sensitivity using an Organic Field‐Effect Transistor

“…Development of analytical methods for biomarkers such as proteins and peptides has great significance in the fields of clinical diagnostics, environmental monitoring, food safety tests, and proteomics . Immunoassays, which are those of the most common methods for protein analyses, can sensitively detect desired analytes, because proteins are recognized through antigen–antibody interactions in measurement systems.…”