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 intratum or injection has low toxicity and thus can be readily combined with existin g treatments. Post-injection gene expression can be documented and occurs i n the presence of an anti-adenovirus immune response. Importantly, this tre atment can cause tumor regression or prolonged stabilization. Future resear ch directions will include development of more efficient vectors, use of no vel genes, and combined modality approaches. Unresectable tumors are a prom inent problem in oncology, with proven therapies such as radiotherapy and c hemotherapy controlling less than 20% of lung cancers. Based on the preclin ical and clinical studies discussed, it now seems that these conventional t herapies may provide renewed potential when used in conjunction with transf er of a functional p53 gene.