Cancer
In vitro, cell culture and mouse studies identified a SALL4-derived peptide inhibitor of the SALL4-RBBP4 interaction that could help treat hepatocellular carcinoma (HCC). Chemical synthesis and in vitro testing of analogs of a SALL4-derived peptide yielded a compound that inhibited SALL4-RBBP4 binding with an IC50 of 23 nM. In three HCC cell lines expressing high levels of SALL4, the peptide decreased viability compared with vehicle. In a xenograft mouse model of HCC, the compound decreased tumor growth and increased survival compared with Nexavar sorafenib or vehicle. Also in the model and in a xenograft mouse model of chemotherapy-resistant HCC, the compound plus Nexavar decreased tumor growth compared with either agent alone. Next steps could include testing the compound in additional HCC models...