biostudies-literatureUnknown26(6)Zapatero-Solana E<h4>Background</h4>CDK4/6 inhibitors (CDK4/6i) combined with hormone therapies have demonstrated clinical benefit in HR+, HER2- breast cancer patients. However, the onset of resistance remains a concern and highlights a need for therapeutic strategies to improve outcomes. The objective of this study was to develop an in vitro model to better understand the mechanisms of resistance to CDK4/6i + hormone therapies and identify therapeutic strategies with potential to overcome this resistance.<h4>Methods</h4>The HR+, HER2- T47D breast cancer cell line genetically modified with a Geminin-Venus reporter construct was treated with CDK4/6i (abemaciclib or palbociclib) in combination with 4-hydroxytamoxifen (tamoxifen). Resistant cells were identified by cell sorting for Geminin (%GEM+), a marker oInternational journal of molecular sciences2643https://www.ebi.ac.uk/biostudies/studies/S-EPMC11942273biostudies-literatureModels of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.PMC11942273Ding YPulliam NLallena MJde Dios AZapatero-Solana EOrtiz-Ruiz MJfalseModels of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.<h4>Background</h4>CDK4/6 inhibitors (CDK4/6i) combined with hormone therapies have demonstrated clinical benefit in HR+, HER2- breast cancer patients. However, the onset of resistance remains a concern and highlights a need for therapeutic strategies to improve outcomes. The objective of this study was to develop an in vitro model to better understand the mechanisms of resistance to CDK4/6i + hormone therapies and identify therapeutic strategies with potential to overcome this resistance.<h4>Methods</h4>The HR+, HER2- T47D breast cancer cell line genetically modified with a Geminin-Venus reporter construct was treated with CDK4/6i (abemaciclib or palbociclib) in combination with 4-hydroxytamoxifen (tamoxifen). Resistant cells were identified by cell sorting for Geminin (%GEM+), a marker o2025-01-01T00:00:00Z2025 Mar2026-05-23T03:22:46.619Z2025-07-02T03:04:39.42ZS-EPMC119422734014128210.3390/ijms26062643