Dataset Information

Overcoming cancer therapeutic bottleneck by drug repurposing.

ABSTRACT: Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing, the development of old drugs for new therapeutic purposes. This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease, facilitating rapid clinical translation. With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches, drug repurposing further promotes the holistic productivity of drug discovery and reasonably focuses on target-defined antineoplastic compounds. The "treasure trove" of non-oncology drugs should not be ignored since they could target not only known but also hitherto unknown vulnerabilities of cancer. Indeed, different from targeted drugs, these old generic drugs, usually used in a multi-target strategy may bring benefit to patients. In this review, aiming to demonstrate the full potential of drug repurposing, we present various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono- or drug combination therapy. We also summarize approaches used for drug repurposing and discuss the main barriers to its uptake.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7331117 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Overcoming cancer therapeutic bottleneck by drug repurposing.

Zhang Zhe Z Zhou Li L Xie Na N Nice Edouard C EC Zhang Tao T Cui Yongping Y Huang Canhua C

Signal transduction and targeted therapy 20200702 1

Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing, the development of old drugs for new therapeutic purposes. This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease, facilitating rapid clinical translation. With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches, drug repurposing fu ...[more]

PMID: 32616710

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Project description:Owing to the limited regenerative capacity of articular cartilage, damaged cartilage does not spontaneously heal over time. Various scientific efforts have been made to improve damaged articular cartilage. Nevertheless, no single approach has achieved a promising outcome for the damaged cartilage. Meanwhile, owing to the increasing cost of drug development, drug repositioning has been actively attempted. We aimed to identify the drug that can improve the cartilage defect, using chondrogenesis related microarray data recruited from the Gene Expression Omnibus (GEO) public database. Furthermore, we attempted to experiment using cellular and animal models to verify the cartilage regeneration potential for the identified drug. To screen for drugs that promote cartilage restoring, chondrogenesis related microarray data were collected from the GEO public database. The GSE69110, GSE107649, GSE111822, and GSE116173 datasets from the GEO were used to identify cartilage differentiation-related genes. Differentially expressed genes were identified using StringTie, and drug data were extracted from the Drug-Gene Interaction database. The effect of aripiprazole on cartilage was evaluated in aripiprazole-treated adipose-derived mesenchymal stem cells (ADMSCs) and chondrocyte using qRT-PCR and 3D pellet culture. The cartilage restoring efficacy was verified in vivo by mixing it with a scaffold and introducing it into the artificially damaged cartilage of Sprague-Dawley rats. Next, mRNA was sequenced for mechanistic analysis. As a result, aripiprazole significantly increased the mRNA expression of COL2A1 and SOX9, two cartilage differentiation-related genes, and chondrogenic condensation in vitro. Moreover, it effectively promoted cartilage regeneration in the cartilage defect rat model. Analysis of mRNA sequencing data from chondrocyte treated with aripiprazole, using KEGG and GOBP, indicated that aripiprazole significantly upregulates genes associated with ribosomes and cytoplasmic translation, thus promoting chondrogenesis. In conclusion, we discovered that aripiprazole can effectively improve damaged cartilage, providing a promising approach for cartilage regeneration.

Dataset Information

Overcoming cancer therapeutic bottleneck by drug repurposing.

Publications

Overcoming cancer therapeutic bottleneck by drug repurposing.

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