{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Demirsoy S"],"funding":["Congressionally Directed Medical Research Programs","Melanoma Research Alliance","NCI NIH HHS","Melanoma Research Alliance Young Investigator Award"],"pagination":["2253"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11202171"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(12)"],"pubmed_abstract":["Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given the lack of actionable targets such as ER and HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring high CDK4/6 expression levels, the efficacy of CDK4/6 inhibition in TNBC has been limited due to the emergence of resistance. The resistance to CDK4/6 inhibition is mainly mediated by <i>RB1</i> inactivation. Since our aim is to overcome resistance to CDK4/6 inhibition, in this study, we primarily used the cell lines that do not express <i>RB1</i>. Following a screening for activated receptor tyrosine kinases (RTKs) upon CDK4/6 inhibition, we identified the TAM (Tyro3, Axl, and MerTK) RTKs as a crucial therapeutic vulnerability in TNBC. We show that targeti"],"journal":["Cancers"],"pubmed_title":["Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition."],"pmcid":["PMC11202171"],"funding_grant_id":["R01 CA233844","817204","W81XWH-21-1-0268","#817204","P30 CA125123","R01 CA256911","W81XWH-20-1-0046"],"pubmed_authors":["Glantz MJ","Liu J","Li Y","Jacob NK","Walter V","Tran H","Aregawi D","Olmez I","Demirsoy S","Schell TD","Yang S"],"additional_accession":[]},"is_claimable":false,"name":"Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition.","description":"Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given the lack of actionable targets such as ER and HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring high CDK4/6 expression levels, the efficacy of CDK4/6 inhibition in TNBC has been limited due to the emergence of resistance. The resistance to CDK4/6 inhibition is mainly mediated by <i>RB1</i> inactivation. Since our aim is to overcome resistance to CDK4/6 inhibition, in this study, we primarily used the cell lines that do not express <i>RB1</i>. Following a screening for activated receptor tyrosine kinases (RTKs) upon CDK4/6 inhibition, we identified the TAM (Tyro3, Axl, and MerTK) RTKs as a crucial therapeutic vulnerability in TNBC. We show that targeti","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-04-07T22:49:30.317Z","creation":"2025-06-01T01:39:42.756Z"},"accession":"S-EPMC11202171","cross_references":{"pubmed":["38927958"],"doi":["10.3390/cancers16122253"]}}