ArticlePLoS biology2017
Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
Article in PLoS biology, 2017. 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 38 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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Therapeutic Fasting in Reducing Chemotherapy Side Effects in Cancer Patients: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- The feasibility and safety of fasting-mimicking diet in breast cancer patients with chemotherapy in China.Breast cancer research and treatment · 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
- NNMT promotes acquired EGFR-TKI resistance by forming EGR1 and lactate-mediated double positive feedback loops in non-small cell lung cancer.Molecular cancer · 2025Article
- Intermittent Fasting and Fasting-mimicking Diet: Promising Strategies in Cancer Management.Current medicinal chemistry · 2025Review
- Review
- Take metabolic heterogeneity into consideration when applying dietary interventions to cancer therapy: A review.Heliyon · 2023Review
- Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade.Nature communications · 2023Article
- Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.Cell reports · 2022Article
- Review
- Intermittent Fasting: Potential Utility in the Treatment of Chronic Pain across the Clinical Spectrum.Nutrients · 2022Review
- Liver Metastatic Breast Cancer: Epidemiology, Dietary Interventions, and Related Metabolism.Nutrients · 2022Review
- Circadian rhythms and cancers: the intrinsic links and therapeutic potentials.Journal of hematology & oncology · 2022Review
- Fasting-mimicking diet blocks triple-negative breast cancer and cancer stem cell escape.Cell metabolism · 2021Article
- Inhibition of Aryl Hydrocarbon Receptor Attenuates Hyperglycemia-Induced Hematoma Expansion in an Intracerebral Hemorrhage Mouse Model.Journal of the American Heart Association · 2021Article
- Article
- Article
- Fasting and fasting-mimicking diets for chemotherapy augmentation.GeroScience · 2021Review
- Nutritional Preconditioning in Cancer Treatment in Relation to DNA Damage and Aging.Annual review of cancer biology · 2021Article
- Early growth response 1 (EGR1) activation in initial stages of host-pathogen interactions.Molecular biology reports · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (PKA) to accelerate aging by inhibiting transcription factors Msn2/4. Here, we show that fasting or glucose restriction (GR) regulate PKA and AMP-activated protein kinase (AMPK) to protect against DXR in part by activating the mammalian Msn2/4 ortholog early growth response protein 1 (EGR1). Increased expression of the EGR1-regulated cardioprotective peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart tissue may also contribute to DXR resistance. Our findings suggest the existence of a glucose-PKA pathway that inactivates conserved zinc finger stress-resistance transcription factors to sensitize cells to toxins conserved from yeast to mammals. Our findings also describe a toxic role for drugs widely used in cancer treatment that promote hyperglycemia and identify dietary interventions that reverse these effects.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.