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Cells 2019, 8(2), 150; https://doi.org/10.3390/cells8020150

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

1
Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy
2
Center for Life Nano [email protected], Istituto Italiano di Tecnologia, 00161 Rome, Italy
3
Department of Biochemical Sciences ‘A. Rossi Fanelli’, Sapienza University, 00185 Rome, Italy
4
International Polyamines Foundation—ONLUS—Via del Forte Tiburtino, 98, 00159 Rome, Italy
5
Pasteur Laboratory, Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy
*
Authors to whom correspondence should be addressed.
These Authors contributed equally to this work.
Received: 11 January 2019 / Revised: 6 February 2019 / Accepted: 8 February 2019 / Published: 11 February 2019
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)
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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. View Full-Text
Keywords: Hedgehog; polyamines; medulloblastoma; basal cell carcinoma; d,l-alpha-difluoromethylornithine Hedgehog; polyamines; medulloblastoma; basal cell carcinoma; d,l-alpha-difluoromethylornithine
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Coni, S.; Di Magno, L.; Serrao, S.M.; Kanamori, Y.; Agostinelli, E.; Canettieri, G. Polyamine Metabolism as a Therapeutic Target in Hedgehog-Driven Basal Cell Carcinoma and Medulloblastoma. Cells 2019, 8, 150.

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