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The enzyme that recycles folate so cells can build DNA. Methotrexate blocks it, which is why folinic acid rescue after high-dose methotrexate matters. This dossier gathers the 2 products (0 approved), 87 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
NADPH-dependent reductase maintaining the tetrahydrofolate pool; amplified in methotrexate-resistant cells.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (folate recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Withdrawn or failed |
|---|---|
| Antifolate 1 | |
| Chemotherapy 1 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | Randomized Double-Blind Phase III Trial of Vitamin D3 Supplementation in Patients With Previously Untreated Metastatic Colorectal Cancer (SOLARIS) | - | ||
| 3 | Completed | A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations | - | ||
ESOPEC NCT02509286 | 3 | Positive | Resectable oesophageal adenocarcinoma: perioperative FLOT chemotherapy against CROSS neoadjuvant chemoradiotherapy, each followed by surgery | Perioperative FLOT improved overall survival compared with CROSS chemoradiotherapy in resectable oesophageal adenocarcinoma. | |
PRODIGE 7 NCT00769405 | 3 | Negative | Colorectal peritoneal metastases with a Peritoneal Cancer Index of 25 or less, after complete macroscopic cytoreduction: oxaliplatin HIPEC added or not, with systemic chemotherapy in both arms | Median overall survival 41.7 against 41.2 months (hazard ratio 1.00); more late grade 3 or worse complications with HIPEC. | |
ABC-06 NCT01926236 | 3 | Positive | Advanced biliary tract cancer after progression on gemcitabine and cisplatin: active symptom control with or without modified FOLFOX | Modified FOLFOX plus active symptom control modestly improved overall survival over active symptom control alone. | |
| 3 | Completed | A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807) | - | ||
NAPOLI-1 NCT01494506 | 3 | Positive | Metastatic pancreatic ductal adenocarcinoma after gemcitabine-based therapy at 76 sites in 14 countries: nanoliposomal irinotecan with fluorouracil and folinic acid, nanoliposomal irinotecan alone, or fluorouracil and folinic acid, with overall survival as the primary endpoint | Median overall survival 6.1 months with nanoliposomal irinotecan plus fluorouracil and folinic acid against 4.2 months with fluorouracil and folinic acid (hazard ratio 0.67, 95 percent confidence interval 0.49 to 0.92; p 0.012); monotherapy 4.9 months (hazard ratio 0.99). | |
CONKO-003 (OFF) NCT00786058 | 3 | Positive | Advanced pancreatic cancer progressing during first-line gemcitabine in Germany: oxaliplatin with folinic acid and fluorouracil (OFF) against folinic acid and fluorouracil (FF), with overall survival as the primary endpoint | Median overall survival 5.9 months with OFF against 3.3 months with FF (hazard ratio 0.66, 95 percent confidence interval 0.48 to 0.91; p 0.010); time to progression 2.9 against 2.0 months. | |
EORTC 40983 NCT00006479 | 3 | Mixed | Up to four resectable colorectal liver metastases: six cycles of FOLFOX4 before and six after liver resection, against surgery alone | No overall survival difference at 8.5 years (hazard ratio 0.88); the earlier progression-free survival benefit stands. | |
| 3 | Completed | A Randomised, Double-blind, Phase III Study to Compare the Efficacy and Safety of Cediranib (AZD2171, RECENTIN™) When Added to 5 Fluorouracil, Leucovorin and Oxaliplatin (FOLFOX) or Capecitabine and Oxaliplatin (XELOX) With the Efficacy and Safety of Placebo When Added to FOLFOX or XELOX in Patients With Previously Untreated Metastatic Colorectal Cancer. | - | ||
PRODIGE 4 / ACCORD 11 NCT00112658 | 3 | Positive | Untreated metastatic pancreatic cancer with ECOG performance status 0 or 1 at French centres: FOLFIRINOX every two weeks against weekly gemcitabine, six months recommended in responders, with overall survival as the primary endpoint of the phase 3 part | Median overall survival 11.1 months with FOLFIRINOX against 6.8 months with gemcitabine (hazard ratio 0.57, 95 percent confidence interval 0.45 to 0.73; p below 0.001); progression-free survival 6.4 against 3.3 months; response 31.6 against 9.4 percent. | |
ESPAC-3 NCT00058201 | 3 | Completed | Resected pancreatic ductal adenocarcinoma (and a separate periampullary cohort): six months of adjuvant fluorouracil with folinic acid against gemcitabine, with overall survival as the primary endpoint; an observation arm was dropped when ESPAC-1 showed chemotherapy helped | Median overall survival 23.0 months with fluorouracil plus folinic acid against 23.6 months with gemcitabine (hazard ratio 0.94, p 0.39); treatment-related serious adverse events 14 against 7.5 percent. | |
PETACC-3 NCT00026273 | 3 | Negative | Stage II and III colon cancer after resection: biweekly infusional fluorouracil and leucovorin with or without irinotecan | Five-year disease-free survival 56.7 against 54.3 percent (p=0.106); no overall survival gain. | |
QUASAR ISRCTN82375386 | 3 | Positive | Adjuvant fluorouracil and folinic acid against observation after apparently curative resection of colon or rectal cancer in people whose indication for chemotherapy was unclear; 2,963 of 3,239 (91 percent) had stage II, node-negative disease; 150 centres in 19 countries, enrolled May 1994 to December 2003 | Relative risk of death 0.82 (0.70 to 0.95, p = 0.008) and of recurrence 0.78 (0.67 to 0.91, p = 0.001) with adjuvant fluorouracil and folinic acid; an absolute five-year survival gain of about 3.6 percent in stage II disease. | |
| AVF2107g | 3 | Positive | Previously untreated metastatic colorectal cancer: irinotecan, bolus fluorouracil and leucovorin (IFL) with bevacizumab or with placebo | Median overall survival 20.3 against 15.6 months, hazard ratio 0.66. | |
| ESPAC-1 | 3 | Mixed | Resected pancreatic ductal adenocarcinoma in Europe: a two-by-two factorial randomisation to adjuvant chemoradiotherapy (20 Gy over two weeks with fluorouracil), adjuvant chemotherapy (fluorouracil and folinic acid), both, or observation, with overall survival as the primary endpoint | Five-year survival 21 percent with adjuvant chemotherapy against 8 percent without (p 0.009); 10 percent with chemoradiotherapy against 20 percent without (p 0.05). | |
MOSAIC NCT00275210 | 3 | Positive | Stage II or III colon cancer after curative resection: FOLFOX4 for six months against fluorouracil and leucovorin alone | Three-year disease-free survival 78.2 against 72.9 percent (hazard ratio 0.77); six-year overall survival benefit in stage III only. | |
| Netherlands Cancer Institute HIPEC trial | 3 | Positive | Peritoneal carcinomatosis from colorectal cancer: cytoreductive surgery with mitomycin C hyperthermic intraperitoneal chemotherapy and systemic fluorouracil and leucovorin, against systemic fluorouracil and leucovorin with or without palliative surgery | Median survival 22.3 against 12.6 months (p=0.032), with 8 percent treatment-related mortality. | |
| INT-0116 (Macdonald trial) | 3 | Positive | Resected gastric or gastro-oesophageal junction adenocarcinoma: postoperative fluorouracil-leucovorin with 45 Gy radiotherapy versus observation | Median overall survival 36 vs 27 months (hazard ratio 0.74). | |
| 3 | Recruiting | A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy | - | ||
| 3 | Recruiting | A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer | - | ||
| 3 | Recruiting | A Phase 3, Double-blind, Randomized Study of Zolbetuximab in Combination With Pembrolizumab and Chemotherapy (CAPOX or mFOLFOX6) in First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in Participants Whose Tumors Are HER2-negative, Claudin (CLDN) 18.2-positive and Programmed Death-ligand 1 (PD-L1)-Positive | - | ||
BALLAD NCT02502370 | 3 | Active | Resected stage I to III small bowel adenocarcinoma: an international randomised trial of adjuvant chemotherapy, with observation against fluorouracil and leucovorin (LV5FU2) where the benefit of chemotherapy is uncertain, and LV5FU2 against FOLFOX where chemotherapy is intended, with three-year disease-free survival as the primary endpoint | - | |
| 3 | - | FUDR/Oxaliplatin HAI Plus Irinotecan Chemotherapy vs. FOLFOXIRI Chemotherapy in Treating Initially Unresectable CRCLM | - | ||
| 3 | Planned | HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate Versus Gemcitabine in Combination With Capecitabine as Adjuvant Therapy for Pancreatic Cancer: an Open, Randomized, Multicenter Phase III Trial. | - | ||
| 3 | Recruiting | Irinotecan Hydrochloride Liposome Injection (II) in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate Versus Nab-paclitaxel in Combination With Gemcitabine for First-line Treatment of Metastatic Pancreatic Cancer: an Open, Randomized, Multicenter Phase III Trial. | - | ||
| 3 | Active | A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin | - | ||
| 3 | Recruiting | A Randomized, Open-label, Controlled, Multicenter Phase 3 Clinical Trial of AK104 for Neoadjuvant/Adjuvant Treatment of Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer | - | ||
| 3 | - | CHEMOTHERAPY CHOICES IN ADVANCED COLORECTAL CANCER: A RANDOMISED TRIAL COMPARING 2 DURATIONS AND 3 SYSTEMIC CHEMOTHERAPY REGIMENS IN THE PALLIATIVE TREATMENT OF ADVANCED COLORECTAL CANCER | - | ||
| 3 | Planned | Investigation of Mitomycin C PIPAC - FOLFIRI Combination for Unresectable Appendiceal or Colorectal Peritoneal Metastases Treatment (IMPACT): A Multicenter, Randomized, Open-Label, Phase 3 Trial | - |
No recorded escape route names this target.
No pathway diagram carries this target as a node.
No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"Dihydrofolate reductase" OR ABSTRACT:"Dihydrofolate reductase" OR TITLE:"DHFR" OR ABSTRACT:"DHFR") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Dihydrofolate reductase (DHFR), not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/dhfr.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/dhfr.json. Licence CC BY-NC 4.0.