Fluorouracil in oral and maxillofacial surgery

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that interferes with DNA synthesis in rapidly proliferating cells, leading to apoptosis and inhibition of cellular proliferation. Traditionally used in the treatment of malignancies such as Basal Cell Carcinoma (BCC) and actinic keratosis, 5-FU has recently been explored for the management of Odontogenic KeratoCyst (OKC) and ameloblastoma. The drug acts as a thymidylate synthase inhibitor, thereby disrupting the cell cycle and promoting tumor cell death. Studies have demonstrated that topical application of 5-FU following surgical enucleation of OKC significantly reduces recurrence rates and minimizes postoperative complications such as permanent paraesthesia, compared to conventional chemical cauterization techniques. At the molecular level, the role of 5-FU relates to the inhibition of signaling pathways associated with PTCH1 gene mutations, which are implicated in both BCC and OKC pathogenesis through activation of the Smoothened (SMO) and Sonic Hedgehog (SHH) pathways. These findings highlight 5-FU as a promising adjunctive therapeutic option for OKC, offering a targeted, conservative, and effective approach to reduce recurrence and morbidity in affected patients.