Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients

Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer

“…ENOF1 catalyzes the dehydration of L-fuconate to 2-keto-3-deoxy-L-fuconate by extracting the 2-proton, generating an enediolate intermediate stabilized by the presence of magnesium ion [ 32 , 33 ]. Although the role of ENOF1 in the mechanism of action of FP is not fully understood, the ENOSF1 gene has been extensively studied for its influence on the toxicity and effectiveness of FP-based treatments [ 18 , 32 , 34 , 35 ]. The rationale for investigating this gene is based on its location in the genome and its potential effects on proteins that are formally related to the PD of FP.…”

“…This observation underscores the need for further exploration in understanding the functional details underlying ENOSF1 [ 39 ]. The ENOSF1 rs2612091 variant (g.683607C>T), located in the intronic region of the gene, has been associated with ENOSF1 mRNA expression and FP-therapy outcomes [ 18 , 32 , 34 , 35 ]. In our study, we observed that patients carrying genotype ENOSF1 rs2612091-TT exhibited superior DFS compared to C allele carriers.…”

“…However, our findings contrasted with those reported by Arjmandi et al (Middle Eastern population; Iran; n = 97) in a study involving gastric cancer patients treated with neoadjuvant 5-FU-based therapy. The researchers reported that the ENOSF1 rs2612091-CC genotype was linked to an increased response to 5-FU compared to the T allele ( p = 0.017) [ 18 ]. These contradictory findings may be explained by differences in the ethnicities of the populations studied, the type of therapeutic regimen under investigation, and the sample sizes of the studies.…”

“…Therefore, apart from TYMS , the genes involved in the folate cycle and DNA repair pathways play an important role in the PD of capecitabine ( Figure 1 ) [ 8 ]. Indeed, numerous studies have investigated the impact of several SNPs in genes related to capecitabine’s PD, such as TYMS , enolase superfamily member 1 gene ( ENOSF1 ), methylenetetrahydrofolate reductase gene ( MTHFR ), ERCC excision repair 1, endonuclease non-catalytic subunit gene ( ERCC1 ), ERCC excision repair 2, TFIIH core complex helicase subunit gene ( ERCC2 ), X-ray repair cross-complementing 1 gene ( XRCC1 ), and X-ray repair cross-complementing 3 gene ( XRCC3 ) on the effectiveness of FP therapy in gastrointestinal neoplasms [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. However, the available evidence remains limited and characterized by conflicting findings, necessitating further investigation and exploration.…”

Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm?

“…The association of ENOSF1 rs2612091 polymorphism with FP-induced toxicity was later replicated by a study in a cohort of 239 CAP-treated patients showing that ENOSF1 rs2612091 was associated with HFS (OR = 2.28) ( García-González et al, 2015 ). Further studies have shown that ENOSF1 rs2612091 is associated with shorter overall survival ( Meulendijks et al, 2017 ) and treatment non-response ( Arjmandi et al, 2022 ), whereas ENOSF1 / TYMS rs699517 polymorphism was associated with CAP-induced severe nausea/vomiting, anorexia and fatigue ( Pellicer et al, 2017 ). A meta-analysis of ENOSF1 rs2612091 association with FP-induced toxicity has demonstrated that ENOSF1 rs2612091 was associated with severe HFS (OR = 1.64) independently of TYMS variants ( Hamzic et al, 2020 ).…”