Our data indicate HDAC10-mediated deacetylation of exogenous polyamines as an alternative source of tumor-supporting polyamines capable of bypassing polyamine-limiting therapies, such as DFMO, emphasizing the need to consider this pathway in the design of polyamine-blocking strategies and suggesting that HDAC10-specific inhibitors may be a beneficial addition to such strategies in certain contexts. This evidence concerns the gene HDAC10 and neoplasm.