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all-trans-retinoic acid + oxaliplatin + fluorouracil + leucovorin
- Development stage
- Unknown
- Lead developer
- Sanofi
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This is a four-drug combination regimen consisting of all-trans-retinoic acid (ATRA), oxaliplatin, fluorouracil (5-FU), and leucovorin. The combination is primarily investigated for the treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastases. All-trans-retinoic acid is a retinoid that induces cell differentiation and apoptosis by binding to nuclear retinoic acid receptors, modulating gene expression involved in cell growth and maturation. Oxaliplatin is a platinum-based chemotherapeutic agent that forms DNA crosslinks leading to apoptosis. Fluorouracil inhibits thymidylate synthase, disrupting DNA synthesis in rapidly dividing cells. Leucovorin enhances the cytotoxic effects of fluorouracil by stabilizing its binding to thymidylate synthase. This regimen has been shown in clinical trials to improve overall survival and time to progression compared with standard FOLFOX4 chemotherapy alone in patients with advanced HCC[1][2][3][9].
- Other names
- ATRA + FOLFOX4all-trans retinoic acid plus FOLFOX4ATRA plus oxaliplatin/fluorouracil/leucovorin
02
Targets
RARA (Retinoic acid receptor alpha)TS (Thymidylate synthase)DNA
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