Targeting Proliferative Capacity in CIC-DUX4 Sarcoma
CIC-DUX4 sarcoma (CDS) belongs to the undifferentiated round cell sarcoma family and is similar in its morphological phenotype to Ewing sarcoma. Affecting mainly pediatric patients, CDS is aggressive and metastatic in its course. The prognosis for these individuals is poor, resulting in a need for continued research of therapeutic methods. E1A-binding protein (P300) and cyclic AMP response element-binding protein (CBP) are histone acetyl transferases vital to oncogenesis in CIC-DUX4. Thus, inhibiting the binding of P300/CBP should limit oncogenesis. In this project, CBP/P300 inhibitors were used, which have shown promise in targeting proliferation of CDS. The compounds were tested over multiple durations on two different CDS cell lines: KITRA and NCC-CDS-X1. All conditions received treatment for 14 consecutive days. Afterwards, treatment was stopped in half of the samples. The cells from all conditions were then analyzed for markers of proliferation every four days. Immunostaining of the cells enabled quantification of the nuclei (via DAPI) and of Ki-67, a protein present during proliferation. Markers of proliferation were also evaluated by qPCR. Visualization of the results showed varying effects of the compounds, with one compound manifesting as very effective. The observations made have important implications in the future of therapeutic treatment of CIC-DUX4 in pediatric patients, with the goal of improving the current, adverse prognosis.