Deng Kaiwen, Li Hongyang, Guan Yuanfang
Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
iScience. 2020 Feb 21;23(2):100804. doi: 10.1016/j.isci.2019.100804. Epub 2019 Dec 26.
Prostate cancer is the most common cancer in men in the Western world. One-third of the patients with prostate cancer will develop resistance to hormonal therapy and progress into metastatic castration-resistant prostate cancer (mCRPC). Currently, docetaxel is a preferred treatment for mCRPC. However, about 20% of the patients will undergo early therapeutic failure owing to adverse events induced by docetaxel-based chemotherapy. There is an emergent need for a computational model that can accurately stratify patients into docetaxel-tolerable and docetaxel-intolerable groups. Here we present the best-performing algorithm in the Prostate Cancer DREAM Challenge for predicting adverse events caused by docetaxel treatment. We integrated the survival status and severity of adverse events into our model, which is an innovative way to complement and stratify the treatment discontinuation information. Critical stratification biomarkers were further identified in determining the treatment discontinuation. Our model has the potential to improve future personalized treatment in mCRPC.
前列腺癌是西方世界男性中最常见的癌症。三分之一的前列腺癌患者会对激素治疗产生耐药性,并进展为转移性去势抵抗性前列腺癌(mCRPC)。目前,多西他赛是mCRPC的首选治疗方法。然而,约20%的患者会因多西他赛化疗引起的不良事件而出现早期治疗失败。迫切需要一种计算模型,能够准确地将患者分为多西他赛耐受组和多西他赛不耐受组。在此,我们展示了前列腺癌DREAM挑战赛中预测多西他赛治疗引起的不良事件的最佳算法。我们将不良事件的生存状态和严重程度整合到模型中,这是一种补充和分层治疗中断信息的创新方法。在确定治疗中断时进一步鉴定了关键分层生物标志物。我们的模型有可能改善未来mCRPC的个性化治疗。