Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy.

TLDR

Polyamine metabolism drives mammalian cell proliferation and is dysregulated in cancer, making the polyamine‑biosynthetic pathway an attractive target for antitumor agents. The study aims to block polyamine biosynthesis at every step of the pathway. The authors evaluate the effect of inhibitors alone and in combination with each other or other antitumor drugs to fully assess this strategy. Polyamine depletion suppresses neoplastic cell growth in vitro and in animal models.

Abstract

The polyamine-biosynthetic pathway represents an inviting target for the development of agents inhibiting carcinogenesis and tumor growth. Polyamines play an essential role in the proliferation and development of mammalian cells. Deranged polyamine metabolism may be an important factor in carcinogenesis. Depletion of polyamines inhibits growth of neoplastic cells in vitro and in animal models. Several different classes of other anticancer agents may under some conditions exert enhanced effects when polyamine levels are depleted. Some suitable inhibitors of polyamine production are currently available and other promising compounds are presently being tested. It should soon prove possible to block polyamine biosynthesis at every step in the pathway. The use of these inhibitors alone and combined either with each other or with other antitumor agents will enable a full examination of the potential of this approach.