Comparative Analysis of CDK4/6 Inhibitors (Ribociclib and Palbociclib) combined with Enzalutamide in Triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) is recognized as a challenging subtype due to its poor prognosis. Recent molecular profiling studies have unveiled a significant subset expressing the androgen receptor (AR) subset which may respond to AR-blocking agents, offering a potentially effective treatment strategy. This study aims to investigate the potential synergistic cytotoxic and apoptotic effects of the AR antagonist enzalutamide (ENZA) in combination with CDK4/6 inhibitors palbociclib (PB) or ribociclib (RB) and compare the effectiveness of these combinations in TNBC cells. Results revaled that ENZA in combination with PB or RB induced synergistic cytotoxic cytotoxicity in all tested TNBC cell lines. While synergistic cytotoxic combinations of ENZA with PB did not induce apoptosis in any TNBC cell line, ENZA+RB combinations exhibited a synergistic apoptotic effect. This study suggests that the ENZA+RB combination may be more favorable due to its apoptosis-inducing effect. However, these data need to be further supported by detailed in vivo and clinical studies