Aamir Mehmood, Mohd Sajid Ali, Daixi Li, Aman Chandra Kaushik, Dong-Qing Wei
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引用次数: 0
摘要
乳腺癌(BC)是导致全球妇女高死亡率的主要原因之一。虽然在治疗策略设计和药物发现方面取得了进展,但耐药性仍是主要挑战之一。克服耐药性的方法之一是寻找潜在的药物组合,因为如果是一对协同作用的组合,联合用药的疗效会高于单个药物的疗效。因此,目前的研究使用了一种 BC 患者衍生异种移植(PDX)数据集,以评估各种抗癌药物对乳腺癌体内模型的影响。通过四种机器学习模型,即弹性网(Elastic Net)、最小绝对收缩和选择(LASSO)、支持向量机(SVM)和随机森林(RF),进一步验证了药物效果,并探索了入围药物与紫杉醇(一种基线药物)联合使用对缩小肿瘤体积的增强疗效。此外,该研究还筛选出了与药物效果相关的前 50 种体内生物标志物。这些成果对设计有效的抗乳腺癌疗法具有重要意义。
Unveiling the Therapeutic Potential of Paclitaxel Combinations Against Breast Carcinoma and Identification of In Vivo Biomarkers
Breast cancer (BC) is one of the leading causes of high mortality rates in women worldwide. Although advancements have been made in the design of therapeutic strategies and drug discovery, drug resistance remains one of the key challenges. One of the ways to overcome drug resistance is finding potential drug combinations since the efficacy of combined drugs is higher than their individual efficacies if the combination is a synergistic pair. Therefore, the current study uses a BC patient-derived xenograft (PDX) dataset to evaluate the effects of various cancer drugs on breast cancer in vivo models. The drug effects are further validated by four machine learning models, namely Elastic Net, Least Absolute Shrinkage and Selection (LASSO), Support Vector Machine (SVM), Random Forests (RF), as well as exploring the shortlisted drugs in combination with paclitaxel, a baseline drug for enhanced efficacy on tumor volume reduction. Additionally, the study also shortlists the top 50 in vivo biomarkers correlated with the effects of the drugs. The outcomes could be significantly important for the design of an effective anti-breast cancer therapy.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.