P53 gene replacement for cancer--interactions with DNA damaging agents.

Clinical trials of p53 gene replacement have provided information that will be useful in the design of future gene therapy strategies. Direct intratumor injection has low toxicity and thus can be readily combined with existing treatments. Post-injection gene expression can be documented and occurs in the presence of an anti-adenovirus immune response. Importantly, this treatment can cause tumor regression or prolonged stabilization. Future research directions will include development of more efficient vectors, use of novel genes, and combined modality approaches. Unresectable tumors are a prominent problem in oncology, with proven therapies such as radiotherapy and chemotherapy controlling less than 20% of lung cancers. Based on the preclinical and clinical studies discussed, it now seems that these conventional therapies may provide renewed potential when used in conjunction with transfer of a functional p53 gene.