p53: Prospettive per la terapia genica dei tumori

Purpose: To evaluate the prospects for cancer gene therapy through restoration of wild-type p53 (wt-p53) protein expression and/or function. Design: To review the most significant data reported in the literature with particular attention in dissecting the biological questions that are still open and need to be clarified to improve TP53-based gene therapy. Results: Considerable experimental evidence obtained in vitro and in vivo indicates that wt-p53 protein can suppress the transformed phenotype of several types of cancer in humans as well as other species. Wt-p53 protein suppress transformation by inducing different biological effects including maintenance of genomic stability, inhibition of cell proliferation, induction of apoptosis, differentiation or senescence. All these findings have rendered p53 a potential helpful target for therapy of many types of human cancers. Conclusions: Different experimental strategies based on i) TP53 gene-replacement, ii) restoration of wt-p53 activity, iii) replication of defective lytic viruses specifically in altered p53-expressing tumors, have given promising results in vitro and, in some cases also in vivo. At present, a few phase one clinical trials have been started for some of the gene-replacement strategies.