EZH2 Inhibition in Triple-Negative Breast Cancer Reduces Tumor Growth

A study sought to determine if the combination treatment of dopamine D1 receptor agonist (A77636) and EZH2 inhibitors (GSK126) inhibits tumor growth and metastasis of triple-negative breast cancer (TNBC). The results were presented at the 2024 San Antonio Breast Cancer Symposium.

Researchers assessed the combination of GSK126 and A77636 in inhibiting in vivo model system. To confirm the findings they used an invitro 3D culture system and 3D organ-on-chip-based micro physiological (MPS) platform SynTumor. Subsequently, 4-6 weeks old female NSG mice were injected with MDA-MB-231 cells on the breast fat pads. The investigators noted that he tumors became palpable, they were randomized into four groups, Vehicle, GSK126 (2mg/kg BW), A77637 (50mg/kg BW) and the combination.

The results showed that the combination of GSK126 and A77636 demonstrated a synergistic effect inhibiting the tumor weight and tumor volume when compared to the individual treatments or the vehicle treated animals. These results, as noted by the researchers, matched with in-vitro data, where the combination synergistically inhibited the growth of spheroids.

“Our data indicate that the combinatorial effect of DRD1 agonist and EZH2 inhibitor efficiently attenuates the EZH2-mediated tumor growth and innate immune environment in TNBC,” the researchers concluded.

Reference

Shankar E, Shukla R, Sarathy G, et al. Enhancer of zeste homologue 2 (EZH2) inhibition in Triple Negative Breast Cancer (TNBC) attenuates tumor growth in vitro and in vivo altering the tumor immune microenvironment. Abstract #SESS-1936. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-13, San Antonio, Texas.