{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["72"],"submitter":["Barghi F"],"pubmed_abstract":["Osteosarcoma (OS) in pediatric, adolescent, and young adult (AYA) patients is an aggressive bone cancer with limited treatment options. Dysregulation of the CDK4/6-cyclin D axis and the PI3K/mTOR pathway contributes to OS pathogenesis, providing a biological rationale for co-targeting these signaling nodes. However, pharmacologic CDK4/6 inhibition can trigger compensatory activation of the PI3K/mTOR pathway, restoring D-type cyclin expression and partially reactivating CDK4/6 signaling. Thus, dual inhibition of the CDK4/6 and PI3K/mTOR pathways not only addresses two parallel oncogenic drivers but may also prevent potential CDK4/6 inhibitor resistance mediated by feedback activation of PI3K/mTOR. In this study, we tested the hypothesis that coordinated targeting of these pathways would imp"],"journal":["Neoplasia (New York, N.Y.)"],"pagination":["101266"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12830294"],"repository":["biostudies-literature"],"pubmed_title":["Dual CDK4/6-PI3K/mTOR inhibition reinforces cytostatic programs and tumor control in preclinical models of primary and metastatic osteosarcoma."],"pmcid":["PMC12830294"],"pubmed_authors":["Collier CD","Young C","Stevens LK","Doud E","Bailey BJ","Sinn AL","Trowbridge MA","Liu S","Sandusky G","Koenig J","Seiden EE","Sulayman S","Just M","Barghi F","Ferguson MJ","Davis C","Wan J","Greenfield EM","Mosley A","Riyahi N","Kreklau K","Pollok KE","Kennedy FM","Malko R","Angus SP","Saadatzadeh MR","Shannon HE","Pandya PH","Bijangi-Vishehsaraei K","Justice R","Jackson KW","Dobrota EA","Coy K","Wurtz LD","Mitchell D"],"additional_accession":[]},"is_claimable":false,"name":"Dual CDK4/6-PI3K/mTOR inhibition reinforces cytostatic programs and tumor control in preclinical models of primary and metastatic osteosarcoma.","description":"Osteosarcoma (OS) in pediatric, adolescent, and young adult (AYA) patients is an aggressive bone cancer with limited treatment options. Dysregulation of the CDK4/6-cyclin D axis and the PI3K/mTOR pathway contributes to OS pathogenesis, providing a biological rationale for co-targeting these signaling nodes. However, pharmacologic CDK4/6 inhibition can trigger compensatory activation of the PI3K/mTOR pathway, restoring D-type cyclin expression and partially reactivating CDK4/6 signaling. Thus, dual inhibition of the CDK4/6 and PI3K/mTOR pathways not only addresses two parallel oncogenic drivers but may also prevent potential CDK4/6 inhibitor resistance mediated by feedback activation of PI3K/mTOR. In this study, we tested the hypothesis that coordinated targeting of these pathways would imp","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-06T22:00:56.256Z","creation":"2026-06-05T03:12:04.512Z"},"accession":"S-EPMC12830294","cross_references":{"pubmed":["41544376"],"doi":["10.1016/j.neo.2025.101266"]}}