2015 Antineoplastics

Question 25

One reason that methotrexate (MTX) followed by leucovorin rescue is effective in treating childhood leukemias is that cancer cells: Answer

  1. are more capable of polyglutaminating MTX, and polyG-MTX binds more potently to dihydrofolate reductase (DHFR).
  2. have a mutated form of DHFR, making them more susceptible to inhibition by MTX.
  3. have impaired folate transport, making them already deficient in tetrahydrofolate and more susceptible to DHFR inhibition.
  4. are more effective in using leucovorin, increasing the binding of MTX to thymidylate synthase.
  5. have higher intracellular pH, promotoing excretion of the drug from the cell.
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM