Molecular mechanisms of drug resistance in tumours
作者:
David J. Harrison,
期刊:
The Journal of Pathology
(WILEY Available online 1995)
卷期:
Volume 175,
issue 1
页码: 7-12
ISSN:0022-3417
年代: 1995
DOI:10.1002/path.1711750103
出版商: John Wiley&Sons, Ltd.
关键词: Drug resistance;mdr1;cytochrome P450;glutathione;topoisomerase;p53;apoptosis;cancer chemotherapy
数据来源: WILEY
摘要:
AbstractDespite advances in the design and use of chemotherapeutic drugs, the majority of human cancers are resistant to therapy at presentation or become resistant after an initial partial response. This suggests that resistance may be inherent in a tumour cell or may evolve under the selection pressure of drug administration. A number of possible molecular explanations for drug resistance exist. There may be exclusion of drug from the cell, failure to activate the prodrug to its active form, increased detoxification, alteration in the drug target, enahanced repair capability of the cell after injury, or failure to engage an appropriate response, leading to apoptosis in the damaged cell. Many of these factors may co‐existin vivoin human tumours; some are a feature of cell lineage whilst others appearde novoduring disease progression. Modulation of these mechanisms has been of some value in laboratory studies but widespread clinical application and benefit remain some way of
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