ArticleCancer research2022
Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 91 citations in OpenAlex.
- Screening Biomarkers Related to Circadian Rhythm of Gastric Cancer Through Bioinformatics.Applied biochemistry and biotechnology · 2026Article
- Review
- Glycolysis‑driven immunosuppression in gastric cancer: Metabolic crosstalk between tumor cells and the immune microenvironment (Review).International journal of oncology · 2026Review
- TRIM32-mediated ubiquitination of STING promotes glycolysis and tumor progression.Cell death and differentiation · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- RHOJ derived peptide promotes chemosensitivity by inhibiting glutamine metabolism in gastric cancer.Journal of translational medicine · 2026Article
- Mechanisms of Metabolic Reprogramming Regulating Immunosuppression in the Gastric Cancer Tumor Microenvironment.Biomolecules · 2026Review
- Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications.Biomedicines · 2026Review
- Glycolytic reprogramming in precancerous lesions of gastric cancer progression: pathogenesis and therapeutic potential.Frontiers in oncology · 2026Review
- Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer.International journal of general medicine · 2026Article
- Metabolic reprogramming as a key regulator in Helicobacter pylori-infected gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Review
- Circadian clock and cancer.Military Medical Research · 2026Review
- Glial Connexin-43 Is a Pathogenic Mechanism Promoting Gut Inflammation in Postoperative Ileus Induced by Gut Surgical Manipulation With Potential Relevance to Humans.Cellular and molecular gastroenterology and hepatology · 2026Article
- Gut Microbiota-induced Long Non-coding RNA Snhg9 Regulates the Development of Human Malignant Tumors.Current molecular medicine · 2026Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.Annals of medicine · 2025Review
- Role of the period family in mediating the interplay between circadian disruption and cancer (Review).Oncology letters · 2025Review
- Haoya Wang Et Al.: Circadian Rhythm Disruption Promotes Tumor Progression Through Upregulated Glycolysis.Cancer medicine · 2025Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab is the only approved targeted drug for first-line treatment of HER2-positive advanced gastric cancer, but the high rate of primary resistance and rapid emergence of secondary resistance limit its clinical benefits. We found that trastuzumab-resistant (TR) gastric cancer cells exhibited high glycolytic activity, which was controlled by hexokinase 2 (HK2)-dependent glycolysis with a circadian pattern [higher at zeitgeber time (ZT) 6, lower at ZT18]. Mechanistically, HK2 circadian oscillation was regulated by a transcriptional complex composed of PPARγ and the core clock gene PER1. In vivo and in vitro experiments demonstrated that silencing PER1 disrupted the circadian rhythm of PER1-HK2 and reversed trastuzumab resistance. Moreover, metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, significantly improved trastuzumab efficacy in gastric cancer. Collectively, these data introduce the circadian clock into trastuzumab therapy and propose a potentially effective chronotherapy strategy to reverse trastuzumab resistance in gastric cancer. SIGNIFICANCE: In trastuzumab-resistant HER2-positive gastric cancer, glycolysis fluctuates with a circadian oscillation regulated by the BMAL1-CLOCK-PER1-HK2 axis, which can be disrupted with a metformin-based chronotherapy to overcome trastuzumab resistance.
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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.