title: RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy.
abstract: Inactivation of the retinoblastoma (RB1) tumor suppressor is one of the most frequent and early recognized molecular hallmarks of cancer. RB1, although mainly studied for its role in the regulation of cell cycle, emerged as a key regulator of many biological processes. Among these, RB1 has been implicated in the regulation of apoptosis, the alteration of which underlies both cancer development and resistance to therapy. RB1 role in apoptosis, however, is still controversial because, depending on the context, the apoptotic cues, and its own status, RB1 can act either by inhibiting or promoting apoptosis. Moreover, the mechanisms whereby RB1 controls both proliferation and apoptosis in a coordinated manner are only now beginning to be unraveled. Here, by reviewing the main studies assessing the effect of RB1 status and modulation on these processes, we provide an overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts. We also describe the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer. A thorough understanding of RB1 function in controlling cell fate determination is crucial for a successful translation of RB1 status assessment in the clinical setting.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.|Department of Medicine, Surgery and Neuroscience, University of Siena and Istituto Toscano Tumori (ITT), Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Indovina
authors.affiliation: Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Tumori "Fodazione G. Pascale" - IRCCS, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pentimalli
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena and Istituto Toscano Tumori (ITT), Siena, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Casini
authors.affiliation: Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Tumori "Fodazione G. Pascale" - IRCCS, Naples, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Vocca
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.|Department of Medicine, Surgery and Neuroscience, University of Siena and Istituto Toscano Tumori (ITT), Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016160:Retinoblastoma Protein
keywords: CDK inhibitors; E2F; RB family; apoptosis; cancer therapy