Stanford University School of Medicine, Division of Oncology, Departments of Medicine and Pathology , Stanford, CA , USA
Expert Opin Investig Drugs. 2013 Nov;22(11):1495-509. doi: 10.1517/13543784.2013.829453. Epub 2013 Aug 12.
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.
Rigosertib（ON01910.Na）是一种靶向治疗药物，可抑制多种激酶，包括 PI3K 和 PIk-1。研究发现，Rigosertib 可诱导髓母细胞增殖停滞和凋亡，但不会影响其他正常造血细胞。Rigosertib 作为治疗高危骨髓增生异常综合征患者的药物具有显著的临床活性，这些患者对 DNA 甲基转移酶抑制剂有耐药性。此外，Rigosertib 在多种实体瘤中有潜在的临床活性。
本综述旨在评估 rigosertib 的作用机制、疗效和剂量。此外，还讨论了 rigosertib 临床开发面临的挑战，以确定最有可能从这种治疗药物中获益的特定患者。使用以下关键词在 PubMed 上进行了搜索：rigosertib 和 ON01910.Na。
我们描述了一种新型纳米尺度蛋白质组学测定法——纳米免疫测定法的应用，该方法是一种可行的方法，可使用有限的人类临床标本实时测量 rigosertib 的活性并预测其疗效。我们的策略表明，在治疗的临床前和临床开发过程中进行蛋白质组学分析，可以用于发现生物标志物，分析和预测人类患者的疗效。
