Polyamine Metabolism as a Therapeutic Target in Hedgehog-Driven Basal Cell Carcinoma and Medulloblastoma

Abstract

Hedgehog (Hh) signaling is a critical developmental regulator and its aberrant activation, due to somatic or germline mutations of genes encoding pathway components, causes Basal Cell Carcinoma (BCC) and medulloblastoma (MB). A growing effort has been devoted at the identification of druggable vulnerabilities of the Hedgehog signaling, leading to the identification of various compounds with variable efficacy and/or safety. Emerging evidence shows that an aberrant polyamine metabolism is a hallmark of Hh-dependent tumors and that its pharmacological inhibition elicits relevant therapeutic effects in clinical or preclinical models of BCC and MB. We discuss here the current knowledge of polyamine metabolism, its role in cancer and the available targeting strategies. We review the literature about the connection between polyamines and the Hedgehog signaling, and the potential therapeutic benefit of targeting polyamine metabolism in two malignancies where Hh pathways play a well-established role: BCC and MB.

Keywords

• Hedgehog
• polyamines
• medulloblastoma
• basal cell carcinoma
• d,l-alpha-difluoromethylornithine%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <span style="font-variant: small-caps">d</span>,<span style="font-variant: small-caps">l</span>-alpha-difluoromethylornithine