[p53: prospects for gene therapy of cancer].
OBJECTIVE
To evaluate the prospects for cancer gene therapy through restoration of wild-type p53 (wt-p53) protein expression and/or function.


METHODS
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.
Soddu
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Laboratorio di Oncogenesi Molecolare, Istituto Regina Elena, Roma, Italia.
Sacchi
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D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D016158:Genes, p53; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy
p53: prospettive per la terapia genica dei tumori.