Which anticancer drug inhibits dihydrofolate reductase?
💡 Explanation
**Core Concept:** Dihydrofolate reductase (DHFR) is an enzyme that plays a crucial role in the synthesis of pyrimidines, purines, and methionine in cells. Inhibition of DHFR impairs DNA and RNA synthesis, ultimately leading to cell cycle arrest and cell death in rapidly dividing cancer cells.
**Why the Correct Answer is Right:** Leucovorin (B) is a folate analogue and a DHFR inhibitor. It works as a rescue agent for methotrexate-induced folate depletion and prevents its toxic effects on normal cells. Methotrexate (D) is another folate analogue and a potent inhibitor of DHFR, used in the treatment of various cancers.
**Why Each Wrong Option is Incorrect:**
A. Hydroxyurea (C) is a DNA synthesis inhibitor used to treat certain types of cancer and blood disorders, but it does not specifically target DHFR.
Option A and B are correct because they are folate analogues and DHFR inhibitors. However, they have distinct applications and mechanisms of action. Leucovorin acts as a rescue agent for methotrexate, while methotrexate is a potent inhibitor of DHFR.
**Clinical Pearl:** Methotrexate and leucovorin form the basis of a combination chemotherapy regimen called "leucovorin rescue" or "leucovorin rescue protocol." This protocol is used in the treatment of certain cancers and blood disorders, where methotrexate is administered and followed by leucovorin administration to prevent methotrexate-induced toxicities while preserving its anticancer effects.