title: Molecules that target nucleophosmin for cancer treatment: an update.
abstract: Nucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review.
authors.affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Di Matteo
authors.affiliation: Dipartimento di Scienze Mediche, Orali e Biotecnologiche, Università di Chieti "G. d'Annunzio", Chieti, Italy.|Ce.S.I.-MeT Centro Scienze dell'Invecchiamento-Medicina Traslazionale, Università di Chieti "G. d'Annunzio",  Chieti, Italy.
authors.forename: Mimma
authors.initials: M
authors.lastname: Franceschini
authors.affiliation: Dipartimento di Scienze Mediche, Orali e Biotecnologiche, Università di Chieti "G. d'Annunzio", Chieti, Italy.|Ce.S.I.-MeT Centro Scienze dell'Invecchiamento-Medicina Traslazionale, Università di Chieti "G. d'Annunzio",  Chieti, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Chiarella
authors.affiliation: Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università di Roma "Sapienza", Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Rocchio
authors.affiliation: Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università di Roma "Sapienza", Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Travaglini-Allocatelli
authors.affiliation: Dipartimento di Scienze Mediche, Orali e Biotecnologiche, Università di Chieti "G. d'Annunzio", Chieti, Italy.|Ce.S.I.-MeT Centro Scienze dell'Invecchiamento-Medicina Traslazionale, Università di Chieti "G. d'Annunzio",  Chieti, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Federici
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use; D015394:Molecular Structure; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D017386:Sequence Homology, Amino Acid
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C000716967:NPM1 protein, human; C530616:NSC 348884; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: B23; acute myeloid leukemia; nucleophosmin; solid tumours; targeted therapy