ArticleJournal of the National Cancer Institute2019
Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 99 citations in OpenAlex.
- Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Integrated transcriptomic and molecular docking analysis identifies Rhotekin 2 as a promising therapeutic target for overcoming gemcitabine resistance in cholangiocarcinoma.Biomedical reports · 2026Article
- Review
- Tegavivint triggers TECR-dependent nonapoptotic cancer cell death.Nature chemical biology · 2025Article
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Pan-cancer analysis of role of LOXL4 and experiment validation in osteosarcoma.Discover oncology · 2025Article
- Impact of scaffold material choice on osteosarcoma phenotype and drug responses in 3D.Acta biomaterialia · 2025Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Review
- Analysis of the effects of acetyl tributyl citrate on bone cancer based on network toxicology and molecular docking.Frontiers in medicine · 2025Article
- Tissue-engineered patient-derived osteosarcoma models dissecting tumour-bone interactions.Cancer metastasis reviews · 2024Review
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Targeting WNT5B and WNT10B in osteosarcoma.Oncotarget · 2024Review
- State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?Journal of mammary gland biology and neoplasia · 2024Review
- Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeted therapies in hepatocellular carcinoma: past, present, and future.Frontiers in oncology · 2024Review
- DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis.iScience · 2023Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe Wnt/β-catenin pathway is closely associated with osteosarcoma (OS) development and metastatic progression. We investigated the antitumor activity of Tegavivint, a novel β-catenin/transducin β-like protein 1 (TBL1) inhibitor, against OS employing in vitro, ex vivo, and in vivo cell line and patient-derived xenograft (PDX) models that recapitulate high risk disease.
methodsThe antitumor efficacy of Tegavivint was evaluated in vitro using established OS and PDX-derived cell lines. Use of an ex vivo three-dimensional pulmonary metastasis assay assessed targeting of β-catenin activity during micro- and macrometastatic development. The in vivo activity of Tegavivint was evaluated using chemoresistant and metastatic OS PDX models. Gene and protein expression were quantified by quantitative Reverse transcription polymerase chain reaction or immunoblot analysis. Bone integrity was determined via microCT. All statistical tests were two-sided.
resultsTegavivint exhibited antiproliferative activity against OS cells in vitro and actively reduced micro- and macrometastatic development ex vivo. Multiple OS PDX tumors (n = 3), including paired patient primary and lung metastatic tumors with inherent chemoresistance, were suppressed by Tegavivint in vivo. We identified that metastatic lung OS cell lines (n = 2) exhibited increased stem cell signatures, including enhanced concomitant aldehyde dehydrogenase (ALDH1) and β-catenin expression and downstream activity, which were suppressed by Tegavivint (ALDH1: control group, mean relative mRNA expression = 1.00, 95% confidence interval [CI] = 0.68 to 1.22 vs Tegavivint group, mean = 0.011, 95% CI = 0.0012 to 0.056, P < .001; β-catenin: control group, mean relative mRNA expression = 1.00, 95% CI = 0.71 to 1.36 vs Tegavivint group, mean = 0.45, 95% CI = 0.36 to 0.52, P < .001). ALDH1high PDX-derived lung OS cells, which demonstrated enhanced metastatic potential compared with ALDHlow cells in vivo, were sensitive to Tegavivint. Toxicity studies revealed decreased bone density in male Tegavivint-treated mice (n = 4 mice per group).
conclusionsTegavivint is a promising therapeutic agent for advanced stages of OS via its targeting of the β-catenin/ALDH1 axis.
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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 OpenQuestion graph.