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Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer.
Real-time nanoscale proteomic analysis of the novel multi-kinase pathway inhibitor rigosertib to measure the response to treatment of cancer. Expert opinion on investigational drugs Fan, A. C., O'Rourke, J. J., Praharaj, D. R., Felsher, D. W. 2013; 22 (11): 1495-1509Abstract
Rigosertib (ON01910.Na), is a targeted therapeutic that inhibits multiple kinases, including PI3K and PIk-1. Rigosertib has been found to induce the proliferative arrest and apoptosis of myeloblasts but not of other normal hematopoietic cells. Rigosertib has significant clinical activity as a therapy for patients with high-risk myelodysplastic syndrome who are otherwise refractory to DNA methyltransferase inhibitors. Moreover, rigosertib has potential clinical activity in a multitude of solid tumors.The objective of this review is to evaluate the mechanism of activity, efficacy and dosing of rigosertib. Furthermore, the challenge in the clinical development of rigosertib, to identify the specific patients that are most likely to benefit from this therapeutic agent, is discussed. A PubMed search was performed using the following key words: rigosertib and ON01910.Na.We describe the application of a novel nanoscale proteomic assay, the nanoimmunoassay, a tractable approach for measuring the activity and predicting the efficacy of rigosertib, in real-time, using limited human clinical specimens. Our strategy suggests a possible paradigm where proteomic analysis during the pre-clinical and clinical development of a therapy can be used to uncover biomarkers for the analysis and prediction of efficacy in human patients.
View details for DOI 10.1517/13543784.2013.829453
View details for PubMedID 23937225