Multidrug resistance in cancer: role of ATP–dependent transporters

Development of inhibitors of ATP-binding cassette transporters should focus on potency and specificity to minimize unexpected pharmacokinetic effects

Michael M. Gottesman

2002

Scholarcy highlights

  • Development of inhibitors of ATP-binding cassette transporters should focus on potency and specificity to minimize unexpected pharmacokinetic effects
  • MULTIDRUG RESISTANCE Simultaneous resistance to several structurally unrelated drugs that do not have a common mechanism of action
  • Selection of cancer cells in culture with natural-product anticancer drugs, such as paclitaxel, doxorubicin, or vinblastine, frequently results in multidrug resistance that is due to expression of the ABC transporter PGP, the product of the ABCB1 gene
  • It seems likely that cancer cells use several different types of ABC transporter to gain drug resistance, most clinical studies have focused on PGP
  • Interpretation of clinical trials involving inhibitors of MDR1/PGP has been confounded by their effects on the pharmacokinetics of anticancer drugs
  • The finding that mice expressing Mdr from a retroviral vector developed myelodysplasia indicates that more needs to be known about the effects of drug-resistance genes on normal haematopoietic function before this approach can be undertaken routinely in cancer patients

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