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The FLOT regimen represents a multi-agent chemotherapy protocol targeting several distinct cellular components to treat gastric and gastroesophageal junction cancers (Al-Batran et al., 2019). It comprises Fluorouracil (5-FU), Leucovorin (Folinic acid), Oxaliplatin, and Docetaxel. Fluorouracil, potentiated by Leucovorin, targets the enzyme thymidylate synthase to inhibit pyrimidine synthesis and DNA repair (StatPearls, 2023). Oxaliplatin acts as a cytotoxic agent by forming bulky DNA adducts and cross-links, which interfere with DNA replication and transcription (PubChem, 2024). Docetaxel targets the protein beta-tubulin within microtubules, promoting their assembly and inhibiting disassembly, which results in mitotic arrest and apoptosis (National Cancer Institute, 2023). Together, these actions disrupt DNA integrity and mitosis, ultimately triggering programmed cell death in rapidly dividing cancer cells.
The FLOT regimen exerts its effects through a multi-targeted approach: Fluorouracil inhibits thymidylate synthase to disrupt DNA synthesis; Oxaliplatin forms DNA adducts that cause intra- and inter-strand cross-links; Docetaxel binds to and stabilizes microtubules, preventing their disassembly and halting mitosis; and Leucovorin enhances the binding of Fluorouracil to its target enzyme (Al-Batran et al., 2019; StatPearls, 2023; PubChem, 2024).
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