title: The TP73 complex network: ready for clinical translation in cancer?
abstract: TP73 is a member of the TP53 family, whose deregulated expression has been reported in a wide variety of cancers and linked to patients' outcome. The fact that TP73 encodes a complex number of isoforms (TAp73 and ΔTAp73) with opposing functions and the cross-talk with other members of the family (TP53 and TP63) make it difficult to determine its clinical relevance. Here, we review the molecular mechanisms driving TAp73 and ΔTAp73 expression and how these variants inhibit or promote carcinogenesis. We also highlight the intricate interplay between TP53 family members. In addition, we comment on current pharmacological approaches targeting the TP73 pathway and those affecting the TAp73/ΔTAp73 ratio. Finally, we discuss the current data available in the literature that provide evidence on the role of TP73 variants in predicting prognosis. To date, most of the studies that evaluate the status levels of TP73 isoforms have been based on limited-size series. Despite this limitation, these publications highlight the correlation between high levels of the oncogenic forms and failure to respond to chemotherapy and/or shorter survival. Finally, we emphasize the need for studies to evaluate the significance of combining the deregulation of various members of the TP53 family in order to define patient outcome or their responsiveness to specific therapies.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Soldevilla
authors.forename: Coral San
authors.initials: CS
authors.lastname: Millán
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D015398:Signal Transduction; D057170:Translational Research, Biomedical; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins