Impact of Phosphoproteomics in the Era of Precision Medicine for Prostate Cancer

Abstract

Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach. Immunohistochemistry and reverse phase protein arrays are limited by the availability of reliable antibodies and evaluates a preselected number of targets. Mass spectrometry-based phosphoproteomics has been used to profile tumors consisting of thousands of phosphopeptides from individual patients after surgical resection or at autopsy. However, this approach is time consuming, and while a large number of candidate phosphopeptides are obtained for evaluation, limitations are reduced reproducibility, sensitivity, and precision. Targeted mass spectrometry can help eliminate these limitations and is more cost effective and less time consuming making it a practical platform for future clinical testing. In this review, we discuss the use of phosphoproteomics in prostate cancer and other clinical cancer tissues for target identification, hypothesis testing, and possible patient stratification. We highlight the majority of studies that have used phosphoproteomics in prostate cancer tissues and cell lines and propose ways forward to apply this approach in basic and clinical research. Overall, the implementation of phosphoproteomics via targeted mass spectrometry has tremendous potential to aid in the development of more rational, personalized therapies that will result in increased survival and quality of life enhancement in patients suffering from metastatic castration-resistant prostate cancer.

Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression

“…A network of interactions between JAM-A and a-enolase 49 emphasizes the strong communication with the MM niche environment to allow persistence and sustaining proliferative signaling. Therefore, JAM-A may represent a key factor in the nurturing substrate 50 supporting the evolution of MM.…”

Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes

“…Proteomes of specific protein modifications are also queried with respect to patient stratification, as rapid advancement of targeted MS platforms could be utilized in clinical settings [ 63 , 64 , 65 ]. Separation of aggressive from non-aggressive PCa based on N-glycoproteome seems moderate so far [ 54 ].…”

Post-Translational Modifications That Drive Prostate Cancer Progression

“…Since the mechanisms of resistance to therapy are expected to vary significantly between patients and in individual tumors, another opportunity for prostate cancer management that is based on phosphorylation emerges from phosphoproteome studies. Analyzing phosphoproteomic profiles of cancer patients would contribute to possible patient stratification and this valuable knowledge could be used in the settings of personalized medicine [ 423 ]. Personalized phosphoproteomics or the analysis of signaling networks in individual tumors, advances personalized therapy by discovering biomarkers of pathway activity and therefore, suggesting potential targets [ 424 ].…”