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5-fluorouracil + methyl aminolevulinate
- Development stage
- Unknown
- Lead developer
- Cleveland Clinic
- Modality
- Light/Condition-Responsive Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules
- Administration
- Topical
01
Overview
This combination therapy regimen consists of the sequential application of topical 5-fluorouracil (5-FU) followed by photodynamic therapy (PDT) using methyl aminolevulinate (MAL). 5-fluorouracil is a pyrimidine antimetabolite that inhibits thymidylate synthase, thereby disrupting DNA synthesis and inducing cell death in rapidly dividing dysplastic keratinocytes. Methyl aminolevulinate is a photosensitizing prodrug that is preferentially metabolized into protoporphyrin IX (PpIX) within neoplastic cells. Subsequent activation with red light triggers a photochemical reaction that generates reactive oxygen species (ROS), leading to targeted tissue destruction. The Cleveland Clinic investigated this regimen to determine if 5-FU pretreatment enhances the accumulation of PpIX, thereby improving the efficacy of PDT for treating actinic keratosis, particularly in high-risk populations such as solid organ transplant recipients.
- Brand names
- MetvixiaEfudex
- Other names
- 5-FU + PDT5-fluorouracil + photodynamic therapy5-FU + MAL-PDT
02
Targets
Protoporphyrin IX (PpIX)-sensitized cellular componentsTS (Thymidylate synthase)
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