Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56
Volume 56, Issue -, Pages 85-102Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010715-103111
Keywords
ABCB1; P-glycoprotein; chemotherapy; platinum compounds; multidrug resistance
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Funding
- NATIONAL CANCER INSTITUTE [ZIABC010830] Funding Source: NIH RePORTER
- Intramural NIH HHS Funding Source: Medline
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Resistance to anticancer drugs is a complex process that results from alterations in drug targets; development of alternative pathways for growth activation; changes in cellular pharmacology, including increased drug efflux; regulatory changes that alter differentiation pathways or pathways for response to environmental adversity; and/or changes in the local physiology of the cancer, such as blood supply, tissue hydrodynamics, behavior of neighboring cells, and immune system response. All of these specific mechanisms are facilitated by the intrinsic hallmarks of cancer, such as tumor cell heterogeneity, redundancy of growth-promoting pathways, increased mutation rate and/or epigenetic alterations, and the dynamic variation of tumor behavior in time and space. Understanding the relative contribution of each of these factors is further complicated by the lack of adequate in vitro models that mimic clinical cancers. Several strategies to use current knowledge of drug resistance to improve treatment of cancer are suggested.
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