The Key Role of IP(6)K: A Novel Target for Anticancer Treatments?

Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP(7) has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP(6)K) isoforms regulate IP(7) synthesis in mammals. Genomic deletion or enzymic inhibition of IP(6)K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP(6)K1 could therefore be a useful target in anticancer treatment. Here, we summarize the current understanding that established IP(6)K1 and the other IP(6)K isoforms as possible targets for cancer therapy. However, it will be necessary to determine whether pharmacological inhibition of IP(6)K is safe enough to begin clinical study. The development of safe and selective inhibitors of IP(6)K isoforms is required to minimize undesirable effects.