51-21-8 | Fluorouracil

CAS:51-21-8 | Fluorouracil ,Description

Fluorouracil (5-FU) is a fluorinated pyrimidine analogue that has been used for the treatment of cancer since the 1950s. It is a chemotherapy drug that works by interfering with the synthesis of DNA, thus inhibiting the growth of cancer cells. 5-FU is one of the most commonly used chemotherapeutic drugs and is used in combination with other drugs in the treatment of a variety of cancers, including colorectal, breast, and head and neck cancers.
 

Scientific Research Applications

Mechanisms of Action and Resistance

Fluorouracil acts by interfering with the synthesis of DNA and RNA in cancer cells, primarily through its metabolite, 5-fluoro-2'deoxy-5' monophosphate (FdUMP), which inhibits thymidylate synthase (TS). This inhibition prevents the methylation of deoxyuridylic acid to thymidylic acid, an essential step in DNA synthesis. Research also focuses on overcoming resistance to 5-FU, which can occur due to changes in the metabolic pathways or alterations in TS, such as gene amplification or altered kinetics (Pinedo & Peters, 1988; Zhang et al., 2008).

Biochemical Modulation to Enhance Efficacy

Biochemical modulation of 5-FU aims to enhance its anticancer activity by combining it with other agents, such as folinic acid, to increase the stability of the FdUMP-TS complex, thereby augmenting its inhibitory effect on DNA synthesis. Studies have shown that this approach can significantly improve treatment outcomes in colon cancer (Sobrero et al., 1997).

Pharmacokinetics and Individualized Therapy

Variability in the metabolism of 5-FU, due to factors such as individual differences in the activity of dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for the degradation of 5-FU, has led to research into pharmacokinetic monitoring and individualized dosing strategies. This aims to optimize therapy by adjusting doses based on the metabolic capacity of the patient, potentially reducing toxicity and improving efficacy (Young et al., 1999; Ploylearmsaeng et al., 2006).

Role in Combination Therapy

Combination therapies involving 5-FU, such as FOLFIRI (5-FU, leucovorin, and irinotecan) and FOLFOX (5-FU, leucovorin, and oxaliplatin), have been extensively studied for their effectiveness in treating colorectal cancer. Research indicates that these combinations can significantly prolong survival and improve response rates compared to 5-FU alone, with the sequence of drugs potentially affecting treatment outcomes (Tournigand et al., 2004).

New Frontiers: Oral Prodrugs

The development of oral prodrugs of 5-FU, such as capecitabine, UFT, and S-1, represents a significant advancement in the administration of fluoropyrimidine chemotherapy, offering potential benefits in terms of ease of administration and patient compliance. These prodrugs are designed to improve the therapeutic index of 5-FU by enhancing its bioavailability and reducing systemic toxicity (Malet-Martino & Martino, 2002).

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