TP73, an under-appreciated player in non-hodgkin lymphoma pathogenesis and management

The TP73 gene is a member of the TP53 family with high structural homology to p53 and capable of transactivating p53 target genes. The TP73 gene locus which is highly conserved and complex, encodes for two classes of isoforms TAp73 (tumor suppressor isoforms containing the transactivation domain) and ΔNp73 (oncogenic isoforms, truncated and lacking the transactivation domain) with opposing effects. The balance between TAp73 and Δ Np73 isoforms and their harmony with other members of the TP73 family regulate various cellular responses such as apoptosis, autophagy, proliferation, and differentiation. The transcriptionally active isoforms of p73 are capable of inducing apoptosis in cancer cells independent of p53 status. Unlike p53, p73 is rarely mutated in cancers, however, the ratio of ΔNp73:TAp73 is frequently up-regulated in many carcinomas and is indicative of poor prognosis. Moreover, p73 is an important determinant of chemosensitivity and radiosensitivity, the two major treatment modalities for lymphoma. In the current review, we will provide an overview of recent progress discussing the role of TP73 in cancer, specifically addressing its relevance to lymphomagenesis, progression, therapy resistance, and its potential as a novel therapeutic target.