ArticleScience advances2022
Fasting improves therapeutic response in hepatocellular carcinoma through p53-dependent metabolic synergism.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Targeting aerobic glycolysis combats tyrosine kinase inhibitor resistance of hepatocellular carcinoma.International journal of cancer · 2026Review
- Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Nutrient Restriction Improves the Therapeutic Efficacy of Sorafenib by Inducing Ferroptosis via the NRF2/HO-1/GPX4 Pathway in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Short-term starvation boosts anti-PD-L1 therapy by reshaping tumor-associated macrophages in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2025Article
- Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.Cell research · 2025Article
- [The Role of Fasting-Mimicking Diet in Cancer Therapy: Mechanisms, Challenges, and Clinical Prospects].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- Fasting and fasting-mimicking conditions in the cancer immunotherapy era.Journal of physiology and biochemistry · 2025Review
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- HnRNPR-mediated UPF3B mRNA splicing drives hepatocellular carcinoma metastasis.Journal of advanced research · 2025Article
- Mitochondrial metabolism: A moving target in hepatocellular carcinoma therapy.Journal of cellular physiology · 2025Review
- Nutrient restriction protects against valve interstitial cell calcification by upregulating ubiquitin mediated proteolysis.Frontiers in cardiovascular medicine · 2025Article
- Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice.BMC biology · 2024Article
- Alpha lipoic acid diminishes migration and invasion in hepatocellular carcinoma cells through an AMPK-p53 axis.Scientific reports · 2024Article
- Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomes.Cellular and molecular life sciences : CMLS · 2024Article
- Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis.iScience · 2024Article
- FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma.Nature communications · 2024Article
- Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 3 institutions in 4 countries.
Funding
Abstract
Cancer cells voraciously consume nutrients to support their growth, exposing metabolic vulnerabilities that can be therapeutically exploited. Here, we show in hepatocellular carcinoma (HCC) cells, xenografts, and patient-derived organoids that fasting improves sorafenib efficacy and acts synergistically to sensitize sorafenib-resistant HCC. Mechanistically, sorafenib acts noncanonically as an inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival. Fasting, through reduction in glucose and impeded AKT/mTOR signaling, prevents this Warburg shift. Regulating glucose transporter and proapoptotic protein expression, p53 is necessary and sufficient for the sorafenib-sensitizing effect of fasting. p53 is also crucial for fasting-mediated improvement of sorafenib efficacy in an orthotopic HCC mouse model. Together, our data suggest fasting and sorafenib as rational combination therapy for HCC with intact p53 signaling. As HCC therapy is currently severely limited by resistance, these results should instigate clinical studies aimed at improving therapy response in advanced-stage HCC.
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.