title: Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis.
abstract: Neuroblastoma (NB) is the most common extracranial childhood tumor classified in five stages (1, 2, 3, 4 and 4S), two of which (3 and 4) identify chemotherapy-resistant, highly aggressive disease. High-risk NB frequently displays MYCN amplification, mutations in ALK and ATRX, and genomic rearrangements in TERT genes. These NB subtypes are also characterized by reduced susceptibility to programmed cell death induced by chemotherapeutic drugs. The latter feature is a major cause of failure in the treatment of advanced NB patients. Thus, proper reactivation of apoptosis or of other types of programmed cell death pathways in response to treatment is relevant for the clinical management of aggressive forms of NB. In this short review, we will discuss the most relevant genomic rearrangements that define high-risk NB and the role that destabilization of p53 and p73 can have in NB aggressiveness. In addition, we will propose a strategy to stabilize p53 and p73 by using specific inhibitors of their ubiquitin-dependent degradation. Finally, we will introduce necroptosis as an alternative strategy to kill NB cells and increase tumor immunogenicity.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, Rome 00133, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Nicolai
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, Rome 00133, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pieraccioli
authors.affiliation: Institute of Cell Biology and Neurobiology (IBCN), CNR, Via E. Ramarini 32, Rome 00015, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Peschiaroli
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier 1, Rome 00133, Italy.|Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, PO Box 138, Leicester LE1 9HN, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: ENEA Research Center Casaccia, Laboratory of Biosafety and Risk Assessment, Via Anguillarese, 301, Rome 00123, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Raschellà
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D006801:Humans; D009336:Necrosis / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction