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Int J Biol Sci. 2026 Jul 30;22(13):7003-7017. doi: 10.7150/ijbs.131639. eCollection 2026.
ABSTRACT
The incidence of early-onset colorectal cancer (EO-CRC, 50 years), indicating selective tumor cytotoxicity. In contrast, the therapeutic window for SN38 was preserved in LO-CRC but not in EO-CRC organoids, revealing age-dependent differences in drug sensitivity. Moreover, calcitriol reduced the cytotoxicity of 5-FU and SN38 in normal organoids regardless of patient age, while in tumor organoids this protective effect was restricted to EO-CRC. As a consequence, calcitriol treatment selectively expanded the therapeutic window for 5-FU and SN38 in LO-CRC organoids. Mechanistically, these effects correlated with calcitriol-induced antiproliferative action and transcriptional regulation of drug metabolism-related pathways. Overall, our findings identify age-dependent differences in chemotherapy response and support the importance of maintaining adequate vitamin D status to reduce chemotherapy-associated toxicity.
PMID:42694971 | PMC:PMC13540450 | DOI:10.7150/ijbs.131639