title: Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy             (Review).
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.
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University,                     Wuhan 430071, P.R. China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhong
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Shao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D058990:Molecular Targeted Therapy; D011355:Prodrugs / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D004317:Doxorubicin; D002401:Cathepsin B