Discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using phosphoproteomics

个体化用药需要预测分子靶向药物的疗效，筛选对药物敏感的患者。药物的作用取决于药物参与的生长信号的活性。蛋白质磷酸化对生长信号的活性起着至关重要的作用，本研究旨在建立磷酸化蛋白的综合定量方法，并利用该方法寻找晚期结直肠癌分子靶向药物疗效的预测性生物标志物。我们修改了以前的磷酸化蛋白质组学技术，并成功地在一个实验中确定了30000磷酸肽。这是迄今为止最大的磷酸化蛋白质组学鉴定研究。我们还发现，PDPK1激酶（EGFR信号通路下游的激酶）的活性可能与抗EGFR抗体药物西妥昔单抗的敏感性有关。

For practice of personalized medicine, prediction of molecular target drug effectiveness and selection of sensitive patients to the drug are needed. Effect of drug depends on the activity of growth signals in which the drug is involved. Protein phosphorylation plays a crucial role for the activity of growth signals.We aimed at establishment of comprehensive quantitation method for phosphoproteins and discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using the method. We modified previous phosphoproteomics technologies and succeeded in identification of 30000 phosphopeptides in one experiment. This is the largest study of phosphoproteomics identification to date. We also showed that activity of PDPK1 kinase, a kinase downstream of EGFR signaling pathway, might be involved in sensitivity of an anti-EGFR antibody drug Cetuximab.