Abstract
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC is potentially a drug target for any disease state where rapid growth is a key process leading to pathology. The compound was originally discovered as an anticancer drug, but its effectiveness was disappointing. However, DFMO was successfully developed to treat African sleeping sickness and is currently one of few clinically used drugs to combat this neglected tropical disease. The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa. In recent years, renewed interest in DFMO for hyperproliferative diseases has led to increased research and promising preclinical and clinical trials. This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma.
Highlights
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl)(Figure 1) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis
This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma
Given the importance of the growth-associated factors in neoplasia, these findings suggest that polyamines are oncometabolites that influence tumorigenesis by regulating specific growth factors, and leading to the increase in tumor numbers and tumor growth rates [67]
Summary
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl). An essential downstream function of the polyamine pathway is the hypusination and activation of eukaryotic initiation factor eIF5A, vital for protein synthesis and cellular proliferation [12]. It has been found that ODC activity is increased and polyamines are present at higher concentrations in some solid tumors [11,14]. This has led to ODC inhibition being investigated as a therapeutic strategy for various malignancies, long-term inhibition of this enzyme is challenging due to the rapid turnover and tight regulation of ODC production. The promise of DFMO to combat colon cancer and neuroblastoma will be discussed
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