ArticleScience advances2021
Therapeutic targeting of SLC6A8 creatine transporter suppresses colon cancer progression and modulates human creatine levels.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 78 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- DH-AUTAC induces ferroptosis in colorectal cancer by targeting DHODH for autophagic degradation through KCTD10-SQSTM1 signaling.Journal of gastroenterology · 2026Article
- Artificial mitochondria ameliorates osteoarthritis through restoring cellular energy metabolism homeostasis.Bioactive materials · 2026Article
- Structure-Based Search for Novel Creatine Transporter Inhibitors.ACS medicinal chemistry letters · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Exploring the anti-asthmatic effects of HMM: OVA-induced murine model and multi-target in silico analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Targeting SLC6A8 suppresses tumor growth and enhances ferroptosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2026Article
- Machine learning-powered single-molecule cancer diagnosis using DNA origami tags.Science advances · 2026Article
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Guanidino compounds with native GABA(A) δ receptor selectivity: a tale of homeostatic compensation in δ-KO mice.BMC neuroscience · 2025Article
- Creatine-mediated ferroptosis inhibition is involved in the intestinal radioprotection of daytime-restricted feeding.Gut microbes · 2025Article
- Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma.Molecular oncology · 2025Article
- Creatine Kinase Blockade Disrupts Energy Metabolism and Redox Homeostasis to Suppress Osteosarcoma Progression.International journal of molecular sciences · 2025Article
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of CAF-derived Vitronectin in Promoting Colorectal Cancer Progression and Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
24 authors at 11 institutions in 2 countries.
Funding
Abstract
Colorectal cancer (CRC) is a leading cause of cancer mortality. Creatine metabolism was previously shown to critically regulate colon cancer progression. We report that RGX-202, an oral small-molecule SLC6A8 transporter inhibitor, robustly inhibits creatine import in vitro and in vivo, reduces intracellular phosphocreatine and ATP levels, and induces tumor apoptosis. RGX-202 suppressed CRC growth across KRAS wild-type and KRAS mutant xenograft, syngeneic, and patient-derived xenograft (PDX) tumors. Antitumor efficacy correlated with tumoral expression of creatine kinase B. Combining RGX-202 with 5-fluorouracil or the DHODH inhibitor leflunomide caused regressions of multiple colorectal xenograft and PDX tumors of distinct mutational backgrounds. RGX-202 also perturbed creatine metabolism in patients with metastatic CRC in a phase 1 trial, mirroring pharmacodynamic effects on creatine metabolism observed in mice. This is, to our knowledge, the first demonstration of preclinical and human pharmacodynamic activity for creatine metabolism targeting in oncology, thus revealing a critical therapeutic target.
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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.