Pharmacological resistance

The underlying concept of pharmacological resistance is that the dose of chemotherapy that can be safely given is insufficient to result in an effective concentration of the active drug at its target site. This may be due to:

♦ Toxicity in other organs

♦ Enhanced clearance of drugs

♦ Physical barrier between bloodstream and tumour cells (many tumours have avascular centres)

♦ De novo resistance—tumour does not respond despite full-dose chemotherapy

♦ Acquired resistance—initial response to chemotherapy, then tumour fails to respond and regrows

♦ Combination of de novo and acquired.

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