Intratumoral gene therapy for non-small cell lung cancer: current status and future directions

Major advances in the field of molecular genetics and cancer biology have allowed for the development of rationally designed anti-cancer strategies. When genetic material (DNA or RNA) is used for this purpose, this approach is called gene therapy. Cancer cells are remarkably sensitive to the inhibition of activated oncogenes or replacement of lost tumor suppressor gene (TSG) function. Replacement of lost TSG p53 function has been achieved by the use of recombinant adenoviral vectors (rAdp53) that carry an expression cassette for this gene. Non-small cell lung cancer has been the subject of early clinical trials in which intratumoral injection of rAdp53 has been performed by transthoracic CT-guided injection or bronchoscopy. Gene transfer and p53 transgene expression have been documented in injected tumors as well as the safety and feasibility of this type of gene therapy. Tumor regression has been reported in rAdp53-injected lesions, either alone or in combination with systemic chemotherapy. Randomized controlled studies as well as clear demonstrations of clinical benefit are missing at present. The results of ongoing studies will allow a verdict on the future of first generation rAdp53 gene therapy. For the whole of the field of gene therapy the advent of more efficient and safe gene transfer technology will determine the speed by which this innovative therapeutic modality will meet with clinical success.