Development of PI3K pathway activation status and its application for predicting therapeutic efficacies of PI3-kinase inhibitors

为了探索用于预测PI 3 K抑制剂（包括我们先前开发的ZSTK 474）的功效的诊断生物标志物，我们在一组39种人类癌细胞系（JFCR 39）中检查了通路激活状态和PI 3 K抑制剂的功效，并构建了一个综合数据库（DB）。使用该DB，我们发现磷酸化Akt和KRAS/BRAF突变分别与PI 3 K抑制剂的有效性和无效性显著相关。这些相关性在体内人类肿瘤异种移植物中得到证实，表明它们可以在未来的临床试验中作为预测性生物标志物。

To explore diagnostic biomarkers for predicting the efficacy of PI3K inhibitors including ZSTK474 that we developed previously, we examined the pathway activation status and the efficacy of PI3K inhibitors in a panel of 39 human cancer cell lines(JFCR39), and constructed an integrated database(DB). Using this DB, we found phospho-Akt and KRAS/BRAF mutation prominently correlated with the efficacy and the inefficacy of PI3K inhibitors, respectively. These correlations were confirmed in human tumor xenografts in vivo, suggesting that they could serve as predictive biomarkers in future clinical trials.