Inhibitors of thymidine synthesis can be used as anticancer drugs because
they block DNA synthesis and decrease rates of cell division. One of the
anticancer drugs that inhibits thymidine synthesis is methotrexate, which
targets the enzyme dihydrofolate reductase. This enzyme is required to
generate the thymidylate synthase substrate methylenetetrahydrofolate,
a coenzyme required in the pathway to generate the nucleotide base
thymine. By inhibiting dihydrofolate reductase activity, rapidly dividing
cells cannot synthesize DNA because they lack the required nucleoside
thymidine. Unfortunately, cancer cells treated with methotrexate often
acquire mutations in the enzyme dihydrofolate reductase, which block
methotrexate binding without significantly altering enzymatic activity.
Once cancer cells become resistant to methotrexate, they are able to rapidly
proliferate, causing cancer progression and the recurrence of disease
symptoms.
Everyday BioChem 