title: Targeted cancer therapy with ribosome biogenesis inhibitors: a real possibility?
abstract: The effects of many chemotherapeutic drugs on ribosome biogenesis have been underestimated for a long time. Indeed, many drugs currently used for cancer treatment--and which are known to either damage DNA or hinder DNA synthesis--have been shown to exert their toxic action mainly by inhibiting rRNA synthesis or maturation. Moreover, there are new drugs that have been proposed recently for cancer chemotherapy, which only hinder ribosome biogenesis without any genotoxic activity. Even though ribosome biogenesis occurs in both normal and cancer cells, whether resting or proliferating, there is evidence that the selective inhibition of ribosome biogenesis may, in some instances, result in a selective damage to neoplastic cells. The higher sensitivity of cancer cells to inhibitors of rRNA synthesis appears to be the consequence of either the loss of the mechanisms controlling the cell cycle progression or the acquisition of activating oncogene and inactivating tumor suppressor gene mutations that up-regulate the ribosome biogenesis rate. This article reviews those cancer cell characteristics on which the selective cancer cell cytotoxicity induced by the inhibitors of ribosome biogenesis is based.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brighenti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Treré
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, Bologna, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Derenzini
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012335:RNA, Ribosomal / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012335:RNA, Ribosomal
keywords: cancer chemotherapy; cell cycle; nucleolus; p53; ribosome biogenesis inhibitors