Methotrexate Trexall, Rheumatrex, Otrexup, Rasuvo

What it is

Methotrexate is a folate antimetabolite chemotherapy agent that belongs to the antifolate class of cytotoxic drugs. In colorectal cancer treatment, it is primarily used in combination regimens for metastatic disease, particularly in patients with mismatch repair deficiencies such as MSH2 mutations. The drug is also employed in low-dose metronomic protocols where continuous low-dose administration aims to provide anti-angiogenic effects alongside cytotoxic activity.

How it works

Methotrexate inhibits dihydrofolate reductase, the enzyme responsible for converting dihydrofolate to tetrahydrofolate, which is essential for DNA synthesis and cellular replication. This inhibition depletes the intracellular folate pool, leading to impaired thymidine and purine synthesis, ultimately resulting in cell cycle arrest in S-phase and apoptosis. In metronomic dosing schedules, methotrexate also exhibits anti-angiogenic properties by affecting endothelial cell proliferation.

Molecular targets

Common side effects

Not all are listed, and everyone experiences them differently. If you notice any, tell your care team.