IMPAKT 2017: LAR Subtype of Triple-Negative Breast Cancer and CDK4/6 Inhibition
The luminal androgen receptor (LAR) subtype of triple-negative breast cancer appears to be highly sensitive to cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, based on a presentation by Asghar et al at the recent IMPAKT Breast Cancer Conference (Abstract 44P) in Brussels, Belgium. However, the investigators noted, basal-like cancers tended to be resistant to CDK4/6 inhibition.
The investigators used in vitro assays on 18 triple-negative breast cancer cell lines to quantify their sensitivity to palbociclib and ribociclib. Distinct differences between cell-cycle exit from mitosis between palbociclib-sensitive and -resistant cell lines were noted, and resistant cells had higher levels of cyclin E1. Resistant cells were made sensitive by blocking cyclin E1 activity, suggesting that dysregulation of cyclin E1 expression may be a key determinant of sensitivity to CDK4/6 inhibition.
An ongoing clinical trial is assessing further CDK46 inhibition in triple-negative breast cancer (ClinicalTrials.gov identifier NCT02389842).