Grace Shapiro
Pronouns: She/Her
Research Mentor(s): Monika Burness
Research Mentor School/College/Department: Internal Medicine / Medicine
Program: UROP
Session: Session 5 (2:40pm – 3:30pm)
Authors: Grace Shapiro, Deeksha Sharma, Monika Burness
Abstract
Current therapies for Triple-negative breast cancer (TNBC), such as chemotherapy and radiation, are successful in killing regular tumor cells. Cancer stem cells (CSCs), however, are treatment-resistant, often metastasize, and can differentiate into other types of cells in the tumor microenvironment. BET proteins play a significant role in the survival and growth of CSCs, and the inhibition of these proteins could disrupt the CSCs growth. Previously the Burness lab has demonstrated that BET protein degrader ZBC-260 inhibits tumor cells and CSCs by modulating anti-tumor immunity in TNBC. This project was designed to understand the mechanism behind the anti-stemness action of ZBC-260. We measured the time and concentration dependent effect of ZBC-260 on the growth of tumor and macrophage cells. Our findings show that ZBC-260 significantly inhibits tumor cell growth (p<0.05), even after 24 h at low concentrations without affecting the growth of macrophages. Using Tumor Immune Estimation Resource (TIMER) we found a positive correlation between BET protein expression and TNBC stemness. Furthermore, we explored the correlation of BET and stemness marker genes with the infiltration of macrophages and found that BET proteins were positively correlated with pro-tumor M2 macrophages infiltration. Based on these findings, BET degrader ZBC-260 appears to improve tumor growth by suppressing M2 macrophages. We are currently studying the direct effect of ZBC-260 on M1 and M2 macrophages and how macrophages co-culturing with tumor cells in the presence or absence of the drug affect the tumor cell growth. In the future, more studies are required to determine the role of BET proteins in macrophage interaction with tumor cells and CSCs.
