General concepts / Drug resistance / Multidrug resistance MULTI-DRUG RESISTANCE
as a general mechanism, MDR occurs when giving one cancer drug results in resistance to many drugs (e.g., giving one alkylating agent results in resistance to all alkylating agents)- however, there is one form of MDR that is particularly problematic, because it is a common resistance mechanism for natural products (e.g., plant alkaloids, anthracycline antibiotics), and, therefore, it crosses mechanism classes
- natural product MDR results from increased expression of:
- mdr-1 gene à increased levels of P-glycoprotein
- experimentally, calcium channel blockers (e.g. verapamil) can reverse this resistance
- multidrug resistance proteins (MRP1-9)
- lung resistance protein (LRP)
- mdr-1 gene à increased levels of P-glycoprotein
- natural product MDR results from increased expression of: