- |||||||||| Ibrance (palbociclib) / Pfizer, Verzenio (abemaciclib) / Eli Lilly
Combination of ZEN-3694 with CDK4/6 inhibitors reverses resistance in ER-positive breast cancer (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_2223;
P1b/2a, P2
In spite of the great successes with the currents lines of therapies, the patients still acquire resistance over time and, the development of additional novel therapeutic strategies is needed.The bromodomain and extra-terminal domain (BET) proteins are key epigenetic regulators that interact with acetylated lysine (AcLys) residues of histones or transcription factors, leading to the regulation of gene transcription...To assess the effects of ZEN-3694 in the combination with CDK4/6 inhibitors as a potential therapy in a CDK4/6i resistant population, we have developed a panel of ER+ cell lines resistant to palbociclib or abemaciclib by continuous stepwise exposure to increasing concentrations of CDK4/6 inhibitors...The pathway analysis demonstrated that the combination of ZEN-3694 with CDK4/6 inhibitors led to the strong downregulation of multiple pathways including cell cycle regulation, signaling by Rho family GTPases, STAT3, IL6 and other pathways. We conclude that ZEN-3694 has therapeutic potential in a combination with CDK4/6 inhibitors in ER+ breast cancer patients that developed resistance to endocrine therapies and/or CDK4/6 inhibitors.
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