ArticleMedComm2023
Integrated multiomic analysis and high-throughput screening reveal potential gene targets and synergetic drug combinations for osteosarcoma therapy.
Article in MedComm, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 19 citations in OpenAlex.
- Proteomics in bone malignancies: from bulk profiling to single-cell and ultra-low-input technologies.Journal of translational medicine · 2026Review
- FGF-23 facilitates osteosarcoma metastasis by modulating the miR-4463/LOXL2 axis expression via the ERK, p38, and JNK signaling pathway.International journal of medical sciences · 2026Article
- Decoding osteosarcoma from heterogeneity to precision therapy.Discover oncology · 2025Review
- Engineering Osteosarcoma In Vitro: From Traditional Models to Biofabricated Platforms for Precision Medicine.ACS omega · 2025Review
- Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma.Cancer research communications · 2025Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Current Bioinformatics Tools in Precision Oncology.MedComm · 2025Review
- PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.Signal transduction and targeted therapy · 2025Article
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cooperative blockade of FLT3 and ALK synergistically suppresses growth of osteosarcoma.Oncogene · 2025Article
- Global research trends and emerging themes in osteosarcoma metabolomics: a bibliometric and visualization analysis.Frontiers in molecular biosciences · 2025Article
- Article
- A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.ACS pharmacology & translational science · 2024Article
- PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.Cancer research · 2024Article
- Molecular mechanism of RBM14-mediated promotion of proliferation, migration, and invasion in osteosarcoma.Translational cancer research · 2024Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although great advances have been made over the past decades, therapeutics for osteosarcoma are quite limited. We performed long-read RNA sequencing and tandem mass tag (TMT)-based quantitative proteome on osteosarcoma and the adjacent normal tissues, next-generation sequencing (NGS) on paired osteosarcoma samples before and after neoadjuvant chemotherapy (NACT), and high-throughput drug combination screen on osteosarcoma cell lines. Single-cell RNA sequencing data were analyzed to reveal the heterogeneity of potential therapeutic target genes. Additionally, we clarified the synergistic mechanisms of doxorubicin (DOX) and HDACs inhibitors for osteosarcoma treatment. Consequently, we identified 2535 osteosarcoma-specific genes and several alternative splicing (AS) events with osteosarcoma specificity and/or patient heterogeneity. Hundreds of potential therapeutic targets were identified among them, which showed the core regulatory roles in osteosarcoma. We also identified 215 inhibitory drugs and 236 synergistic drug combinations for osteosarcoma treatment. More interestingly, the multiomic analysis pointed out the pivotal role of HDAC1 and TOP2A in osteosarcoma. HDAC inhibitors synergized with DOX to suppress osteosarcoma both in vitro and in vivo. Mechanistically, HDAC inhibitors synergized with DOX by downregulating SP1 to transcriptionally modulate TOP2A expression. This study provided a comprehensive view of molecular features, therapeutic targets, and synergistic drug combinations for osteosarcoma.
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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.