ArticleCancer research2024
PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- KLF16 promotes immune escape in hepatocellular carcinoma cells by upregulating PD-L1 expression via PRKDC.Translational oncology · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- C/EBP alpha agonist ICCB280 overcomes doxorubicin resistance in osteosarcoma through mitochondrial dynamics-dependent GREM1-MAPK activation.Cell death & disease · 2026Article
- IGF2BP3 promotes glycolysis of osteosarcoma stem cells by reading RNA m⁶A to stabilize ENO1 and promote malignant biological behavior of osteosarcoma.Cell biology and toxicology · 2026Article
- Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.Genome medicine · 2026Article
- Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy.Cell reports. Medicine · 2026Article
- Nicotinamide N-methyltransferase promotes drug resistance in lung cancer, as revealed by nascent proteomic profiling.Molecular oncology · 2026Article
- Emerging research themes in drug resistance in osteosarcoma: a 25-year bibliometric and visualized analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- METTL3-mediated mMolecular cancer · 2026Article
- Neoadjuvant chemotherapy followed by limb-sparing surgery for osteosarcoma: a retrospective cohort study on efficacy, safety, and prognostic factors.American journal of cancer research · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Long non-coding RNAs in osteosarcoma: multifaceted regulators of malignancy and therapeutic resistance.Journal of translational medicine · 2025Review
- Exploring the Tumor Microenvironment in Osteosarcoma: Driver of Resistance and Progression.Cancers · 2025Review
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Enhancing doxorubicin sensitivity in osteosarcoma via iRGD-modified biomimetic nanoparticles targeting MCAM m6A modification.Journal of translational medicine · 2025Article
- Establishment of patient-derived 3D in vitro models of sarcomas: literature review and guidelines on behalf of the FORTRESS working group.Neoplasia (New York, N.Y.) · 2025Review
- A Dual Approach with Organoid and CRISPR Screening Reveals ERCC6 as a Determinant of Cisplatin Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
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9 authors.
Funding
Abstract
Chemoresistance is one of the major causes of poor prognosis in osteosarcoma. Alternative therapeutic strategies for osteosarcoma are limited, indicating that increasing sensitivity to currently used chemotherapies could be an effective approach to improve patient outcomes. Using a kinome-wide CRISPR screen, we identified PRKDC as a critical determinant of doxorubicin (DOX) sensitivity in osteosarcoma. The analysis of clinical samples demonstrated that PRKDC was hyperactivated in osteosarcoma, and functional experiments showed that the loss of PRKDC significantly increased sensitivity of osteosarcoma to DOX. Mechanistically, PRKDC recruited and bound GDE2 to enhance the stability of protein GNAS. The elevated GNAS protein levels subsequently activated AKT phosphorylation and conferred resistance to DOX. The PRKDC inhibitor AZD7648 and DOX synergized and strongly suppressed the growth of osteosarcoma in mouse xenograft models and human organoids. In conclusion, the PRKDC-GDE2-GNAS-AKT regulatory axis suppresses DOX sensitivity and comprises targetable candidates for improving the efficacy of chemotherapy in osteosarcoma. Significance: Targeting PRKDC suppresses AKT activation and increases sensitivity to doxorubicin in osteosarcoma, which provides a therapeutic strategy for overcoming chemoresistance.
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