Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.
1/5 보강
Genomic uracil and its respective repair play key roles in colorectal, gastric, and other solid tumor therapies targeting thymidylate biosynthesis.
APA
Holub E, Papp G, et al. (2026). Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.. Life science alliance, 9(4). https://doi.org/10.26508/lsa.202503352
MLA
Holub E, et al.. "Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.." Life science alliance, vol. 9, no. 4, 2026.
PMID
41651672 ↗
Abstract 한글 요약
Genomic uracil and its respective repair play key roles in colorectal, gastric, and other solid tumor therapies targeting thymidylate biosynthesis. Previously, we established that treating HCT116 colon cancer cell lines with either raltitrexed (RTX) or 5-fluoro-2'-deoxyuridine (5FdUR), two potent inhibitors of thymidylate synthase, results in characteristic genomic uracil patterns. Here, we focus on drug-specific differences in the genomic uracil profiles and their associations with altered cytotoxicity and drug-induced mutagenesis. We demonstrated that biased uracilation preferentially affects functionally related genes in a drug-specific manner, highlighting the biological significance of genomic uracilation. Mutational analysis further revealed a significant increase in the frequency of C-to-T somatic transitions, selectively in response to high-dose 5FdUR treatment, in DNA repair-deficient cells. The mutational spectra and the clustered nature of these transitions suggested the involvement of APOBEC3 DNA cytidine deaminases, several of which were induced under these conditions. Notably, this mutagenic response coincides with decreased cytotoxicity compared with the low-dose 5FdUR or any efficient doses of RTX, providing insights that may be relevant for personalized cancer therapy.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- A Phase I Study of Hydroxychloroquine and Suba-Itraconazole in Men with Biochemical Relapse of Prostate Cancer (HITMAN-PC): Dose Escalation Results.
- Self-management of male urinary symptoms: qualitative findings from a primary care trial.
- Clinical and Liquid Biomarkers of 20-Year Prostate Cancer Risk in Men Aged 45 to 70 Years.
- Diagnostic accuracy of Ga-PSMA PET/CT versus multiparametric MRI for preoperative pelvic invasion in the patients with prostate cancer.
- Association of patient health education with the postoperative health related quality of life in low- intermediate recurrence risk differentiated thyroid cancer patients.
- Early local immune activation following intra-operative radiotherapy in human breast tissue.