Cancer

Patient sample, cell culture and mouse studies suggest inhibiting SMARCA2 or its downstream effector YAP1 could help treat hepatocellular carcinoma (HCC). In patient samples, levels of SMARCA2 and YAP1 were higher in tumors than in surrounding normal tissue, and tumor levels of the two proteins were associated with disease progression. In two human HCC lines and primary tumor cells from six HCC patients, SMARCA2 knockdown or knockout decreased tumorsphere formation compared with normal SMARCA2 expression. In the patients’ cells, YAP1 knockout decreased tumorsphere formation compared with normal YAP1 expression, and in four patients’ cells the YAP1 inhibitor Visudyne verteporfin decreased tumorsphere formation compared with vehicle. In a xenograft mouse model of HCC, tumor-specific knockdown of SMARCA2 or YAP1 decreased tumor growth compared with normal SMARCA2 and YAP1 expression. Next steps could include identifying and testing SMARCA2 or YAP1 inhibitors in HCC models...