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The TP73 complex network: Ready for clinical translation in cancer?
Author(s) -
Soldevilla Beatriz,
Millán Coral San,
Bonilla Félix,
Domínguez Gemma
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22095
Subject(s) - relevance (law) , carcinogenesis , clinical significance , translation (biology) , gene isoform , cancer , biology , bioinformatics , computational biology , medicine , genetics , messenger rna , political science , gene , law
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 Δ TAp73 ) 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 Δ TAp73 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 /Δ TAp73 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. © 2013 Wiley Periodicals, Inc.