Xu Tuan, Ngan Deborah K, Zheng Wei, Huang Ruili
Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, 20850, USA.
Pharmacogenomics J. 2025 Feb 19;25(2):2. doi: 10.1038/s41397-025-00361-6.
The pathogenesis of cancer is complicated, and different types of cancer often exhibit different gene mutations resulting in different omics profiles. The purpose of this study was to systematically identify cancer-specific biological pathways and potential cancer-targeting drugs. We collectively analyzed the transcriptomics and proteomics data from 16 common types of human cancer to study the mechanism of carcinogenesis and seek potential treatment. Statistical approaches were applied to identify significant molecular targets and pathways related to each cancer type. Potential anti-cancer drugs were subsequently retrieved that can target these pathways. The number of significant pathways linked to each cancer type ranged from four (stomach cancer) to 112 (acute myeloid leukemia), and the number of therapeutic drugs that can target these cancer related pathways, ranged from one (ovarian cancer) to 97 (acute myeloid leukemia and non-small-cell lung carcinoma). As a validation of our method, some of these drugs are FDA approved therapies for their corresponding cancer type. Our findings provide a rich source of testable hypotheses that can be applied to deconvolute the complex underlying mechanisms of human cancer and used to prioritize and repurpose drugs as anti-cancer therapies.
癌症的发病机制很复杂,不同类型的癌症通常表现出不同的基因突变,从而导致不同的组学特征。本研究的目的是系统地识别癌症特异性生物学途径和潜在的癌症靶向药物。我们综合分析了16种常见人类癌症类型的转录组学和蛋白质组学数据,以研究致癌机制并寻找潜在的治疗方法。应用统计方法来识别与每种癌症类型相关的重要分子靶点和途径。随后检索了能够靶向这些途径的潜在抗癌药物。与每种癌症类型相关的重要途径数量从4条(胃癌)到112条(急性髓系白血病)不等,能够靶向这些癌症相关途径的治疗药物数量从1种(卵巢癌)到97种(急性髓系白血病和非小细胞肺癌)不等。作为对我们方法的验证,其中一些药物是FDA批准用于其相应癌症类型的疗法。我们的研究结果提供了丰富的可测试假设来源,可用于剖析人类癌症复杂的潜在机制,并用于将药物作为抗癌疗法进行优先排序和重新利用。