State Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
Brief Bioinform. 2024 Mar 27;25(3). doi: 10.1093/bib/bbae121.
As key oncogenic drivers in non-small-cell lung cancer (NSCLC), various mutations in the epidermal growth factor receptor (EGFR) with variable drug sensitivities have been a major obstacle for precision medicine. To achieve clinical-level drug recommendations, a platform for clinical patient case retrieval and reliable drug sensitivity prediction is highly expected. Therefore, we built a database, D3EGFRdb, with the clinicopathologic characteristics and drug responses of 1339 patients with EGFR mutations via literature mining. On the basis of D3EGFRdb, we developed a deep learning-based prediction model, D3EGFRAI, for drug sensitivity prediction of new EGFR mutation-driven NSCLC. Model validations of D3EGFRAI showed a prediction accuracy of 0.81 and 0.85 for patients from D3EGFRdb and our hospitals, respectively. Furthermore, mutation scanning of the crucial residues inside drug-binding pockets, which may occur in the future, was performed to explore their drug sensitivity changes. D3EGFR is the first platform to achieve clinical-level drug response prediction of all approved small molecule drugs for EGFR mutation-driven lung cancer and is freely accessible at https://www.d3pharma.com/D3EGFR/index.php.
作为非小细胞肺癌(NSCLC)中的关键致癌驱动因子,表皮生长因子受体(EGFR)的各种突变具有不同的药物敏感性,这一直是精准医学的主要障碍。为了实现临床级别的药物推荐,非常需要一个用于临床患者病例检索和可靠药物敏感性预测的平台。因此,我们通过文献挖掘,建立了一个包含 1339 名 EGFR 突变患者的临床病理特征和药物反应的数据库,名为 D3EGFRdb。在此基础上,我们开发了一种基于深度学习的预测模型 D3EGFRAI,用于预测新的 EGFR 突变驱动的 NSCLC 的药物敏感性。D3EGFRAI 的模型验证显示,对于来自 D3EGFRdb 和我们医院的患者,其预测准确性分别为 0.81 和 0.85。此外,还对药物结合口袋内可能发生的关键残基进行了突变扫描,以探索其药物敏感性变化。D3EGFR 是第一个实现所有批准的针对 EGFR 突变驱动肺癌的小分子药物的临床级药物反应预测的平台,可在 https://www.d3pharma.com/D3EGFR/index.php 免费访问。