Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy (Review)

Zhong,Yan-Jun; Shao,Li-Hua; Li,Yan

doi:10.3892/ijo.2012.1754

Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy (Review)

Authors:
- Yan-Jun Zhong
- Li-Hua Shao
- Yan Li
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Affiliations: Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
Published online on: December 28, 2012 https://doi.org/10.3892/ijo.2012.1754
Pages: 373-383
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs used for the treatment of hematological malignancies, as well as a broad range of solid tumors. However, the clinical applications of this drug have long been limited due to its severe dose‑dependent toxicities. Therefore, DOX derivatives and analogs have been developed to address this issue. A type of DOX prodrug, cleaved by cathepsin B (Cat B), which is highly upregulated in malignant tumors and premalignant lesions, has been developed to achieve a higher DOX concentration in tumor tissue and a lower concentration in normal tissue, so as to enhance the efficacy and reduce toxicity to normal cells. In this review, we focused on Cat B-cleavable DOX prodrugs and discussed the efficacy of these prodrugs, demonstrated by preclinical and clinical developments.

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