> [!caution]+ > Tumor cells may compensate for HDAC and proteasome inhibition in vivo in ways that are not observed in culture. Pathways may be activated in tumor cells in culture that make them particularly vulnerable to HDAC and proteasome inhibitors, but those pathways may be less vulnerable in vivo. Additional pharmacodynamics studies will be required to distinguish between these possibilities. Our data demonstrate that ex vivo activity does not always translate in vivo, and this is why it is important to perform preclinical phase I, II, and III studies before moving new drug combinations into clinical trials for pediatric solid tumors. > [Source: St Jude](http://www.stjude.org/CSTN/)