{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(36)"],"submitter":["Soria-Bretones I"],"pubmed_abstract":["Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are standard first-line treatments for metastatic ER<sup>+</sup> breast cancer. However, acquired resistance to CDK4/6i invariably develops, and the molecular phenotypes and exploitable vulnerabilities associated with resistance are not yet fully characterized. We developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids and demonstrate that a subset of resistant models accumulates mitotic segregation errors and micronuclei, displaying increased sensitivity to inhibitors of mitotic checkpoint regulators TTK and Aurora kinase A/B. <i>RB1</i> loss, a well-recognized mechanism of CDK4/6i resistance, causes such mitotic defects and confers enhanced sensitivity to TTK inhibition. In these models, inhibi"],"journal":["Science advances"],"pagination":["eabq4293"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9451148"],"repository":["biostudies-literature"],"pubmed_title":["The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER<sup>+</sup> breast cancer with mitotic aberrations."],"pmcid":["PMC9451148"],"pubmed_authors":["Kiarash R","Mak TW","Fletcher GC","El Ghamrasni S","Thu KL","Cheng A","Cruickshank J","Cescon DW","Elliott MJ","Rose AAN","Silvester J","Chalmers JJ","Elia AC","Bray MR","Ba-Alawi W","Soria-Bretones I","Haibe-Kains B"],"additional_accession":[]},"is_claimable":false,"name":"The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER<sup>+</sup> breast cancer with mitotic aberrations.","description":"Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are standard first-line treatments for metastatic ER<sup>+</sup> breast cancer. However, acquired resistance to CDK4/6i invariably develops, and the molecular phenotypes and exploitable vulnerabilities associated with resistance are not yet fully characterized. We developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids and demonstrate that a subset of resistant models accumulates mitotic segregation errors and micronuclei, displaying increased sensitivity to inhibitors of mitotic checkpoint regulators TTK and Aurora kinase A/B. <i>RB1</i> loss, a well-recognized mechanism of CDK4/6i resistance, causes such mitotic defects and confers enhanced sensitivity to TTK inhibition. In these models, inhibi","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-05-28T21:28:12.841Z","creation":"2025-02-19T03:24:31.202Z"},"accession":"S-EPMC9451148","cross_references":{"pubmed":["36070391"],"doi":["10.1126/sciadv.abq4293"]}}