DL-α-Difluoromethylornithine Hydrochloride (DFMO)

Background

The polyamine analog DL-α-Difluoromethylornithine Hydrochloride (DFMO) inhibits the enzyme ornithine decarboxylase (ODC), which catalyzes the rate-limiting step of polyamine biosynthesis. Originally developed to treat excessive hair growth and trypanosomiasis, DFMO was later studied as a potential therapeutic to block the development of cancers that relied on polyamine biosynthesis (1). Blocking polyamine biosynthesis with DFMO in conjunction with the drug-induced inhibition of polyamine uptake prevented or delayed tumor development in neuroblastoma-prone mice, and extended survival in rodent models of established tumors (2). Treatment with DFMO suppressed oncogene MYC expression and MYC-mediated tumorigenesis, and improved treatment of chemoresistant pancreatic ductal adenocarcinoma (3). Inhibition of ODC by DFMO blocked tumor growth in intact immunocompetent mice, but not in immunodeficient individuals. Specifically, DFMO promoted an immunological response to cancer as treatment of mice increased anti-tumor CD8⁺ T cell infiltration and IFN-γ production, augmented the efficacy of adoptive T cell therapy, and impaired myeloid-derived suppressor cell activity (4).