Yuqin Lin , Yanghong Zhu , Xiang Li , Qi Chen , Guoyu Wu
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引用次数: 0
摘要
三阴性乳腺癌(triple negative breast cancer, TNBC)是一种特殊类型的乳腺癌,其ER、PR、HER2均为阴性,具有恶性程度高、侵袭性强、复发率高的特点。开发新的药物来改善三阴性乳腺癌的治疗方法是至关重要的。在这里,我们揭示了与三阴性乳腺癌相关的转录景观,并使用综合连接图确定了候选药物。候选成分可诱导TNBC基因表达特征的反向表达并触发转录重编程,对调节乳腺癌患者的化疗耐药和生存率有积极影响。我们的研究还提供了一个使用计算机药物筛选进行药物发现的例子,随后进行了进一步的验证,说明了一种有效的计算药物发现策略。
Identifying candidate drugs based on transcriptional landscape associated with triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a special type of breast cancer in which ER, PR and HER2 are all negative, characterized by high malignancy, strong invasiveness, and high recurrence rate. It is critical to develop novel drugs for improved therapies for triple-negative breast cancers. Here, we unveiled the transcriptional landscape associated with triple-negative breast cancer and identified candidate drugs using a comprehensive connectivity map. The candidate components could induce reverse expressions of the TNBC gene expression signature and trigger transcriptional reprogramming with a positive impact on modulating chemoresistance and the survival probability of breast cancer patients. Our study also provided an example of drug discovery using in silico drug screening followed by further validations, illustrating an effective computational drug discovery strategy.