biostudies-literatureUnknown10(1)Liu BCisplatin (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, PKMSignal transduction and targeted therapy165https://www.ebi.ac.uk/biostudies/studies/S-EPMC12092789biostudies-literaturePKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.PMC12092789Jin XTu CXu RWan LFu ZXu HFeng CLi WZhang WHe SLiu ZLi ZLiu BfalsePKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.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, PKM2025-01-01T00:00:00Z2025 May2026-06-01T10:22:28.812Z2026-04-08T11:22:55.009ZS-EPMC120927894039398310.1038/s41392-025-02250-7