Kim Youngchul, Dillon Patrick M, Park Taesung, Lee Jae K
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA.
Division of Hematology/Oncology, University of Virginia, Charlottesville, VA, USA.
Oncotarget. 2017 Dec 9;9(1):1091-1106. doi: 10.18632/oncotarget.23124. eCollection 2018 Jan 2.
Many cancer therapeutic agents have shown to be effective for treating multiple cancer types. Yet major challenges exist toward introducing a novel drug used in one cancer type to different cancer types, especially when a relatively small number of patients with the other cancer type often benefit from anti-cancer therapy with the drug. Recently, many novel agents were introduced to different cancer types together with companion biomarkers which were obtained or biologically assumed from the original cancer type. However, there is no guarantee that biomarkers from one cancer can directly predict a therapeutic response in another. To tackle this challenging question, we have developed a concordant expression biomarker-based technique ("CONCORD") that overcomes these limitations. CONCORD predicts drug responses from one cancer type to another by identifying concordantly co-expressed biomarkers across different cancer systems. Application of CONCORD to three standard chemotherapeutic agents and two targeted agents demonstrated its ability to accurately predict the effectiveness of a drug against new cancer types and predict therapeutic response in patients.
许多癌症治疗药物已被证明对多种癌症类型有效。然而,将一种用于某一癌症类型的新药应用于不同癌症类型面临重大挑战,尤其是当相对少数的其他癌症类型患者往往受益于该药物的抗癌治疗时。最近,许多新型药物与从原始癌症类型获得或生物学推断出的伴随生物标志物一起被引入不同癌症类型。然而,来自一种癌症的生物标志物并不能保证直接预测另一种癌症的治疗反应。为了解决这个具有挑战性的问题,我们开发了一种基于共表达生物标志物的技术(“CONCORD”),该技术克服了这些局限性。CONCORD通过识别不同癌症系统中协同共表达的生物标志物来预测从一种癌症类型到另一种癌症类型的药物反应。将CONCORD应用于三种标准化疗药物和两种靶向药物,证明了其准确预测药物对新癌症类型有效性以及预测患者治疗反应的能力。