Targeting the Human 80S Ribosome in Cancer: from Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies
cells Review Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies Arnaud Gilles 1,Léo Frechin 2, Kundhavai Natchiar 2, Giulia Biondani 3, Ottilie von Loeffelholz 2 , Samuel Holvec 2, Julie-Lisa Malaval 1 , Jean-Yves Winum 1,* , Bruno P. Klaholz 2,* and Jean-François Peyron 3,* 1 IBMM, Univ Montpellier, CNRS, IBMM, ENSCM, 34296 Montpellier, France; arnaud.gilles@enscm.fr (A.G.); julie-lisa.malaval@etu.umontpellier.fr (J.-L.M.) 2 Université de Strasbourg, CNRS, Inserm, Centre for Integrative Biology, IGBMC, 67404 Illkirch, France; frechinl@igbmc.fr (L.F.); natchiar@igbmc.fr (K.N.); loeffelc@igbmc.fr (O.v.L.); holvecs@igbmc.fr (S.H.) 3 Université Côte d’Azur, Inserm, C3M, 06204 Nice, France; giulia.biondani88@gmail.com * Correspondence: jean-yves.winum@umontpellier.fr (J.-Y.W.); klaholz@igbmc.fr (B.P.K.); peyron@unice.fr (J.-F.P.) Received: 23 January 2020; Accepted: 2 March 2020; Published: 5 March 2020 Abstract: The human 80S ribosome is the cellular nucleoprotein nanomachine in charge of protein synthesis that is profoundly affected during cancer transformation by oncogenic proteins and provides cancerous proliferating cells with proteins and therefore biomass. Indeed, cancer is associated with an increase in ribosome biogenesis and mutations in several ribosomal proteins genes are found in ribosomopathies, which are congenital diseases that display an elevated risk of cancer. Ribosomes and their biogenesis therefore represent attractive anti-cancer targets and several strategies are being developed to identify efficient and specific drugs. Homoharringtonine (HHT) is the only direct ribosome inhibitor currently used in clinics for cancer treatments, although many classical chemotherapeutic drugs also appear to impact on protein synthesis.
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