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Methotrexate therapy
Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism and reducing DNA synthesis and cell proliferation.
Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism and reducing DNA synthesis and cell proliferation. Used for Acute lymphoblastic leukemia (ALL) in pediatric patients, Osteosarcoma, Rheumatoid arthritis.
At a glance
| Generic name | Methotrexate therapy |
|---|---|
| Sponsor | National Medical Research Center for Children's Health, Russian Federation |
| Drug class | Folate antagonist / Antimetabolite |
| Target | Dihydrofolate reductase (DHFR) |
| Modality | Small molecule |
| Therapeutic area | Oncology, Immunology, Rheumatology |
| Phase | FDA-approved |
Mechanism of action
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, an enzyme critical for converting dihydrofolate to tetrahydrofolate, which is essential for one-carbon transfer reactions in nucleotide synthesis. By depleting intracellular folate cofactors, it suppresses DNA and RNA synthesis, leading to reduced cell proliferation. At lower doses used in rheumatologic and pediatric conditions, it also has immunosuppressive and anti-inflammatory effects through adenosine release and other mechanisms.
Approved indications
- Acute lymphoblastic leukemia (ALL) in pediatric patients
- Osteosarcoma
- Rheumatoid arthritis
- Juvenile idiopathic arthritis
- Various pediatric malignancies
Common side effects
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Mucositis
- Hepatotoxicity
- Nephrotoxicity
- Nausea and vomiting
- Alopecia
- Infection
Key clinical trials
- Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (PHASE2)
- A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (PHASE3)
- Pediatric-Inspired Regimen Combined With Venetoclax and Immunotherapy for Adult Ph-Negative Acute Lymphoblastic Leukemia (NA)
- Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer (PHASE2, PHASE3)
- Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia (PHASE2)
- Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults (PHASE3)
- Venlafaxine as Adjunct Therapy in Rheumatoid Arthritis (PHASE2)
- Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
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