The paper also indicates that CUDC-101 achieves a synergistic effect through simultaneous inhibition of HDAC, EGFR and HER2 targets. The authors tested the growth-inhibitory activity of CUDC-101 in a total of 54 human cancer cell lines, with results showing that the compound effectively inhibits growth of a broad range of cancer cell types, including lung, pancreas, liver, colon, breast, prostate and head and neck. Notably, CUDC-101 exhibited equal or greater potency in these assays than vorinostat (a marketed HDAC inhibitor), erlotinib (a marketed EGFR inhibitor), lapatinib (a marketed EGFR/HER2 inhibitor) and combinations of vorinostat and erlotinib and vorinostat and lapatinib. CUDC-101 also suppressed the growth of the lapatinib-insensitive, triple-negative (estrogen receptor-, progesterone receptor- and HER2-negative) breast cancer cell line MDA-MB-231 as effectively as it did the lapatinib-sensitive, HER2-overexpressed lines BT-474 and SkBr-3. Similarly, CUDC-101 inhibits the growth of lung cancer cell lines that are not sensitive to erlotinib treatment, including H1975, which harbor an EGFR-T790M mutation. These results suggest that CUDC-101, with its synergistic inhibitions of multiple pathways, has the potential to enhance the response rates and prolong the duration of response when compared to traditional kinase inhibitors.

Source Curis, Inc.