Several mechanisms contribute to MDR in cancer cells:
Efflux Pumps: Proteins such as P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs) actively transport a wide variety of drugs out of the cancer cells, reducing their intracellular concentration and effectiveness. Drug Target Modifications: Changes or mutations in the drug targets can render the drugs ineffective. For instance, alterations in topoisomerase, targeted by certain chemotherapy drugs, can lead to resistance. Drug Metabolism: Cancer cells can alter the drug metabolism by enhancing the expression of detoxifying enzymes, which can inactivate the drugs before they exert their cytotoxic effects. DNA Repair Mechanisms: Enhanced DNA repair capabilities allow cancer cells to quickly repair the damage caused by chemotherapeutic agents, thus maintaining their survival. Cell Death Inhibition: Cancer cells can evade apoptosis, the process of programmed cell death, through various pathways, allowing them to survive despite the presence of anti-cancer drugs.
