Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks

被引:4
作者
Qin, Shimei [1 ]
Li, Wan [1 ]
Yu, Hongzheng [1 ]
Xu, Manyi [1 ]
Li, Chao [1 ]
Fu, Lei [1 ]
Sun, Shibin [1 ]
He, Yuehan [1 ]
Lv, Junjie [1 ]
He, Weiming [2 ]
Chen, Lina [1 ]
机构
[1] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Peoples R China
[2] Harbin Inst Technol, Inst Optoelect, Harbin 150001, Peoples R China
基金
中国国家自然科学基金;
关键词
NSCLC; drug repositioning; drug similarity network; Random Walk with Restart; COMBINING ERLOTINIB; PHASE I/II; INHIBITOR; CHEMOTHERAPY; PANITUMUMAB; COMBINATION; DASATINIB; DISCOVERY; CARCINOMA; GROWTH;
D O I
10.3390/ijms24032244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Drug repositioning aims to discover novel clinical benefits of existing drugs, is an effective way to develop drugs for complex diseases such as cancer and may facilitate the process of traditional drug development. Meanwhile, network-based computational biology approaches, which allow the integration of information from different aspects to understand the relationships between biomolecules, has been successfully applied to drug repurposing. In this work, we developed a new strategy for network-based drug repositioning against cancer. Combining the mechanism of action and clinical efficacy of the drugs, a cancer-related drug similarity network was constructed, and the correlation score of each drug with a specific cancer was quantified. The top 5% of scoring drugs were reviewed for stability and druggable potential to identify potential repositionable drugs. Of the 11 potentially repurposable drugs for non-small cell lung cancer (NSCLC), 10 were confirmed by clinical trial articles and databases. The targets of these drugs were significantly enriched in cancer-related pathways and significantly associated with the prognosis of NSCLC. In light of the successful application of our approach to colorectal cancer as well, it provides an effective clue and valuable perspective for drug repurposing in cancer.
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页数:21
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