A young man with leukemia is treated with methotrexate. Which of the following is the mechanism of action of this drug?
**Core Concept**
Methotrexate is an antifolate drug that interferes with DNA synthesis and repair, making it effective against rapidly dividing cells such as cancer cells. It works by inhibiting the enzyme dihydrofolate reductase (DHFR), which is essential for the conversion of dihydrofolate to tetrahydrofolate.
**Why the Correct Answer is Right**
Methotrexate enters the cell and binds to DHFR, preventing the enzyme from converting dihydrofolate to tetrahydrofolate. Tetrahydrofolate is necessary for the synthesis of thymidine and purines, which are essential for DNA replication and repair. By inhibiting DHFR, methotrexate disrupts DNA synthesis and repair, ultimately leading to cell death in rapidly dividing cells. This mechanism of action makes methotrexate effective against a wide range of cancers, including leukemia.
**Why Each Wrong Option is Incorrect**
* **Option A:** Methotrexate does not work by inhibiting the enzyme topoisomerase, which is involved in DNA replication and repair. Topoisomerase inhibitors, such as etoposide, are a different class of cancer chemotherapy drugs.
* **Option B:** Methotrexate does not work by stimulating the immune system. While some cancer treatments do work by stimulating the immune system, methotrexate is an antifolate drug that works by disrupting DNA synthesis and repair.
* **Option D:** Methotrexate does not work by inhibiting the enzyme tyrosine kinase. Tyrosine kinase inhibitors, such as imatinib, are a different class of cancer chemotherapy drugs that target specific tyrosine kinases involved in cancer cell growth and survival.
**Clinical Pearl / High-Yield Fact**
Methotrexate is a classic example of a chemotherapy drug that works by targeting a specific enzyme involved in DNA synthesis and repair. This highlights the importance of understanding the biochemical pathways involved in cancer cell growth and survival.
**Correct Answer: C. Inhibiting dihydrofolate reductase (DHFR) to prevent DNA synthesis and repair.**