Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 42, Issue 2, Pages 373-383Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2012.1754
Keywords
cancer chemotherapy; cathepsin B; doxorubicin; prodrugs; targeted therapy
Categories
Funding
- State Key Research Project on Infectious Diseases [2012ZX10002012-012]
- National Natural Science Foundation of China [81171396]
- National University Students Innovation Training Project of China [101048639]
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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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