期刊
CURRENT OPINION IN PHARMACOLOGY
卷 41, 期 -, 页码 20-26出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.coph.2018.04.004
关键词
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资金
- National Institutes of Health [R35GM 119512]
- NIH National Center for Advancing Translational Sciences [TL1 TR001451, UL1 TR001450]
DNA crosslinking agents make up a broad class of chemotherapy agents that target rapidly dividing cancer cells by disrupting DNA synthesis. These drugs differ widely in both chemical structure and biological effect. In cells, crosslinking agents can form multiple types of DNA lesions with varying efficiencies. Inter-strand crosslinks (ICLs) are considered to be the most cytotoxic lesion, creating a covalent roadblock to replication and transcription. Despite over 50 years in the clinic, the use of crosslinking agents that specialize in the formation of ICLs remains limited, largely due to high toxicity in patients. Current ICL-based therapeutics have focused on late-stage and drug-resistant tumors, or localized treatments that limit exposure. In this article, we review the development of clinical crosslinking agents, our understanding of how cells respond to different lesions, and the potential to improve ICL-based chemotherapeutics in the future.
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