The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis

Mammalian polyamines, including putrescine, spermidine, and spermine, are positively charged amines that are essential for all living cells including neoplastic cells. An increasing understanding of polyamine metabolism, its molecular functions, and its role in cancer has led to the interest in targeting polyamine metabolism as an anticancer strategy, as the metabolism of polyamines is frequently dysregulated in neoplastic disease. In addition, due to compensatory mechanisms, combination therapies are clinically more promising, as agents can work synergistically to achieve an effect beyond that of each strategy as a single agent. In this article, the nature of polyamines, their association with carcinogenesis, and the potential use of targeting polyamine metabolism in treating and preventing cancer as well as combination therapies are described. The goal is to review the latest strategies for targeting polyamine metabolism, highlighting new avenues for exploiting aberrant polyamine homeostasis for anticancer therapy and the mechanisms behind them.