Chemoresistance

Chemoresistance (comparable to antibiotic resistance in bacteria) is the reduced or non-response of tumour cells to a chemotherapeutic agent. Resistance to tumor therapeutic agents usually results from mutations and the subsequent selection of tumor cells with survival advantage. There are different mechanisms for the development of resistance:

• Reduced uptake of the therapeutic agent into the cell (e.g. by reduced expression of the folate transporter in methotrexate)
• Increased DNA repair of cytostatic-induced damage
• Overexpression of target proteins for cytostatic drugs: e.g. dihydrofolate reductase in methotrexate
• Increased inactivation of the cytostatic drug
• Inhibition of apoptosis by overexpression of anti-apoptotic proteins
• Massively increased outward transport of the cytostatic drug out of the cell through overexpression of ABC transporters (e.g. P-glycoprotein transports anthracyclines out of the cell)