Pancreatic adenocarcinoma is a highly malignant cancer that often involves a 
deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the 
regulation of a variety of physiological processes and is involved in early 
neoplastic development, resulting in poor progression. Hence, suppression of 
c-Myc overexpression is a potential strategy for pancreatic cancer therapy. 
CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) 
and histone deacetylase (HDAC). It has shown potential efficiency in patients 
with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors 
with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates 
c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic 
cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently 
inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 
values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor 
mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it 
suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which 
was a mode of action distinct from the existing mechanisms. Consistently, the 
extraordinary antitumor activity of CUDC-907 accompanied by downregulation of 
c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic 
cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that 
CUDC-907 can be a valuable therapeutic option for treating pancreatic 
adenocarcinoma.