ArticleJournal of experimental & clinical cancer research : CR2025
Genomic profiling of a collection of patient-derived xenografts and cell lines identified ixabepilone as an active drug against chemo-resistant osteosarcoma.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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Who cites it
2 citing papers in PubMed.
- LL-37 inhibits osteosarcoma progression by suppressing SQLE-mediated cholesterol synthesis via the PTEN/AKT/mTOR pathway.Journal of bone oncology · 2026Article
- ZEB1 integrates stemness, differentiation blockade and immune suppression to orchestrate osteosarcoma aggressiveness.Journal of experimental & clinical cancer research : CR · 2026Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
backgroundOsteosarcoma (OS) shows a multitude of genetic and chromosomal abnormalities together with large biological heterogeneity. These features limited the identification of novel drugs to treat patients with metastases and/or chemo-resistant tumors. The purpose of this study was to create additional resources for drug screening by generating patient-derived xenograft (PDXs) and PDX-derived cell lines that reflect the spectrum of OS heterogeneity.
methodsPDXs were derived from OS collected at diagnosis, surgical resections, or metastases. PDX-derived cell lines were also established. Targeted DNA sequencing and digital PCR were applied to identify major genetic alterations. High-throughput drug screening by using a library of 2880-FDA approved compounds and conventional MTT assays were performed to identify the most effective drugs against in vitro and in vivo growth of chemo-resistant OS.
resultsTargeted DNA sequencing demonstrated alterations in the most commonly amplified oncogenes, such as MYC, CCNE1, DDR2, CDK4, MDM2, and AURKA. Recurrent deletions and SNVs were found in TP53, CDKN2A, RB1, PTEN, and VHL. Copy number variant (CNV) alterations in PDXs, PDX-derived cell lines and xenografts developed from cell lines (CDX) correlated very well with those observed in the matched original human tumors. Drug screenings identified and repurposed five compounds with efficacy against chemoresistant OS. In this context, we prioritized ixabepilone as a drug capable of inducing tumor regression in mice.
conclusionsWe enriched the scientific community with additional, molecularly characterized OS models to be used for testing novel therapies and supported the inclusion of ixabepilone into treatment plans for chemoresistant OS.
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