Dovitinib 是一种 VEGFR1-3、PDGFR、FGFR1/3、c-KIT、FLT3 和拓扑异构酶1和2 的受体酪氨酸激酶抑制剂。药物反应预测生物标志物算法（DRP）或 DRP-Dovitinib正作为 dovitinib 的伴随诊断试剂进行开发，并且已进行回顾性的应用。该研究中获取了肾细胞癌患者的同意后的存档肿瘤样本，用于对比比较 dovitinib 和索拉非尼的3期试验，并应用了 DRP-Dovitinib。该生物标志物算法结合了与 vitro 对 dovitinib 敏感性或耐药性相关的58条信使RNA的表达，包括与 FGFR、PDGF、VEGF、PI3K/Akt/mTOR 和拓扑异构酶途径以及 ABC 药物转运相关的基因，并提供了0-100%之间的可能性评分。DRP-Dovitinib 将接受 dovitinib 治疗的肾细胞癌患者分为两组，即敏感组（n = 49，DRP 评分 > 50%）和耐药组（n = 86，DRP 评分 ≤ 50%）。将 DRP 敏感人群与未筛选的索拉非尼组（n = 286）进行比较。DRP 敏感 dovitinib组的中位无进展生存期（PFS）为3.8个月，与索拉非尼组的中位无进展生存期（PFS）为3.6个月（风险比0.71，95% CI 0.51-1.01）。DRP 敏感 dovitinib组的中位总生存期（OS）为15.0个月，索拉非尼组为11.2个月（风险比0.69，95% CI 0.48-0.99）。随着 DRP 评分的增加，观察到的临床效益也增加。以67%为截断点，dovitinib 组的中位 OS 为 20.6 个月，中位 PFS 为 5.7 个月。通过对 dovitinib 的五个规模较小的2期试验进行确认，结果显示出类似的趋势。DRP-Dovitinib 有望成为一种潜在的生物标志物，用于识别进展期肾细胞癌患者中最有可能从 dovitinib 治疗中获得临床效益的人群，在需要进一步通过对肾细胞癌患者进行独立前瞻性试验来确认的情况下。版权声明：©2023年Knudsen等人。这是一篇以创作共用许可证发表的开放获取论文，允许任何媒介的自由使用、分发和复制，前提是原作者和来源得到了适当的署名。

Dovitinib is a receptor tyrosine kinase inhibitor of VEGFR1-3, PDGFR, FGFR1/3, c-KIT, FLT3 and topoisomerase 1 and 2. The drug response predictor (DRP) biomarker algorithm or DRP-Dovitinib is being developed as a companion diagnostic to dovitinib and was applied retrospectively.Archival tumor samples were obtained from consenting patients in a phase 3 trial comparing dovitinib to sorafenib in renal cell carcinoma patients and the DRP-Dovitinib was applied. The biomarker algorithm combines the expression of 58 messenger RNAs relevant to the in vitro sensitivity or resistance to dovitinib, including genes associated with FGFR, PDGF, VEGF, PI3K/Akt/mTOR and topoisomerase pathways as well as ABC drug transport, and provides a likelihood score between 0-100%.The DRP-Dovitinib divided the dovitinib treated RCC patients into two groups, sensitive (n = 49, DRP score >50%) or resistant (n = 86, DRP score ≤ 50%) to dovitinib. The DRP sensitive population was compared to the unselected sorafenib arm (n = 286). Median progression-free survival (PFS) was 3.8 months in the DRP sensitive dovitinib arm and 3.6 months in the sorafenib arm (hazard ratio 0.71, 95% CI 0.51-1.01). Median overall survival (OS) was 15.0 months in the DRP sensitive dovitinib arm and 11.2 months in the sorafenib arm (hazard ratio 0.69, 95% CI 0.48-0.99). The observed clinical benefit increased with increasing DRP score. At a cutoff of 67% the median OS was 20.6 months and the median PFS was 5.7 months in the dovitinib arm. The results were confirmed in five smaller phase II trials of dovitinib which showed a similar trend.The DRP-Dovitinib shows promise as a potential biomarker for identifying advanced RCC patients most likely to experience clinical benefit from dovitinib treatment, subject to confirmation in an independent prospective trial of dovitinib in RCC patients.Copyright: © 2023 Knudsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.