ArticleSignal transduction and targeted therapy2025
PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.
Article in Signal transduction and targeted therapy, 2025. 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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Who cites it
17 citing papers in PubMed.
- Bevacizumab induces apoptosis in glioblastoma cells by upregulating miR-4695-5p to inhibit PKMYT1.RNA biology · 2026Article
- An immuno-chemotherapeutic bone scaffold for tumor eradication and bone regeneration in drug-resistant osteosarcoma.Bioactive materials · 2026Article
- E2F3 amplification primes bladder cancer cells for premature mitosis.Cancer gene therapy · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Multi-responsive tetrahedral DNA frameworks forChemical science · 2026Article
- Hyaluronic acid-engineered copper sulfide nanoparticles as immunomodulatory metal sulfide photothermal agents for macrophage-assisted osteosarcoma therapy.Materials today. Bio · 2026Article
- Integrative Transcriptomic and Functional Analysis of PKMYT1 Reveals a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.Hematological oncology · 2026Article
- PKMYT1 in Cancer: Beyond Cell Cycle Checkpoints to Context-Dependent Therapeutic Vulnerability.Genes, chromosomes & cancer · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- KAT2A-IGF2BP1-CXCL2 axis in the high lactate tumor microenvironment facilitates resistance to anti-PD-1 therapy in lung adenocarcinoma by recruiting myeloid-derived suppressor cells.Cell death & disease · 2026Article
- NUDT1 drives osteosarcoma progression and serves as a robust predictor of clinical outcomes.Cancer cell international · 2026Article
- ATR and PKMYT1 Inhibition Resensitizes a Subset of TNBC Patient-Derived Models to Carboplatin, Inducing Mitotic Catastrophe.Cancer research communications · 2026Article
- Genomic mapping reveals cisplatin disruption of protein phosphorylation signalling genome-wide.Metallomics : integrated biometal science · 2026Article
- Targeting PKMYT1 enhances antitumor immune responses to PD-L1 blockade in castration-resistant prostate cancer.Journal for immunotherapy of cancer · 2026Article
- Long non-coding RNAs in osteosarcoma: multifaceted regulators of malignancy and therapeutic resistance.Journal of translational medicine · 2025Review
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Intelligent Nanomedicine Systems Utilizing Diverse Nanoparticles for Osteosarcoma Therapy: A Review.International journal of nanomedicine · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin (DDP) remains a cornerstone therapy for osteosarcoma (OS); however, pervasive resistance severely limits its clinical efficacy and worsens patient outcomes. Developing strategies to enhance the chemotherapeutic responsiveness of OS cells is therefore of critical importance. Here, we conducted a kinome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen, coupled with transcriptome sequencing, to identify regulators of DDP sensitivity. This approach revealed protein kinase membrane-associated tyrosine/threonine 1 (PKMYT1) as a key regulator of DDP sensitivity in OS. Subsequent analysis of patient-derived clinical specimens, along with in vitro functional assays, demonstrated that DDP treatment induces the activation of PKMYT1 in OS cells. Importantly, PKMYT1 silencing markedly enhances cellular sensitivity to DDP, indicating its role in promoting chemoresistance. Mechanistically, PKMYT1 induces phosphorylation of nucleophosmin 1 (NPM1) at the S260 site, which competitively impairs NPM1 SUMOylation. This modification interferes with the recruitment of essential DNA damage response factors, including breast cancer suppressor gene 1 (BRCA1), receptor-associated protein 80 (RAP80), and RADiation sensitive protein 51 (RAD51), ultimately affecting double-strand break (DSB) repair. Furthermore, the selective PKMYT1 inhibitor RP6306 was found to synergize with DDP, amplifying its cytotoxic effects in OS cells. Collectively, these findings highlight PKMYT1 as a promising therapeutic target and provide a rationale for combinatorial strategies to overcome DDP resistance in OS.
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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.