Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.
1/5 보강
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths.
APA
Fekry B, Aggarwal S, et al. (2025). Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.. Cell reports, 44(11), 116313. https://doi.org/10.1016/j.celrep.2025.116313
MLA
Fekry B, et al.. "Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.." Cell reports, vol. 44, no. 11, 2025, pp. 116313.
PMID
41124076 ↗
Abstract 한글 요약
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Most patients present at advanced stages, and the effectiveness of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors is constrained by limited patient response. A subset of HCC shows elevated expression of the promoter 2 ("P2")-driven hepatocyte nuclear factor 4 alpha (HNF4α) isoform, which directly transcriptionally represses the circadian brain and muscle ARNT-like protein 1 (BMAL1) transcription factor. This subtype of HCC is robustly inhibited by the plant-based flavonoid nobiletin (NOB), a circadian-fortifying compound. Using patient-matched human HCC and serum, we show that BMAL1-deficient HCC shows exaggerated carnitine palmitoyl transferase expression and related metabolite abundance and that P2-HNF4α regulates the carnitine palmitoyl transferase I gene. Finally, using different preclinical models, we show that the anti-tumor activity of TKIs, when they are co-administered with NOB, is maximal. Our results suggest that chronotherapy and combination therapy might provide improved clinical outcomes for individuals with BMAL1-deficient HCC.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Carcinoma
- Hepatocellular
- Liver Neoplasms
- Humans
- Circadian Clocks
- Animals
- ARNTL Transcription Factors
- Protein Kinase Inhibitors
- Mice
- Carnitine O-Palmitoyltransferase
- Flavones
- Cell Line
- Tumor
- Liver
- Male
- BMAL1
- CP: Cancer
- CP: Metabolism
- CPT1A
- HNF4α
- acylcarnitine
- chronotherapy
- circadian
- hepatocellular carcinoma
… 외 3개
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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