Joe Putnam
Faculty Member
Last active: 3/27/2014

Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement.

Roth JA, Swisher SG, Merritt JA, Lawrence DD, Kemp BL, Carrasco CH, El-Naggar AK, Fossella FV, Glisson BS, Hong WK, Khurl FR, Kurie JM, Nesbitt JC, Pisters K, Putnam JB, Schrump DS, Shin DM, Walsh GL
Semin Oncol. 1998 25 (3 Suppl 8): 33-7

PMID: 9704675

The identification of genetic lesions that lead a normal cell to become malignant presents us with the opportunity of targeting those lesions as a means of therapy. Given the key role played by the tumor suppressor gene p53 in cell cycle regulation and apoptosis, and the evidence linking p53 mutations with non-small cell lung cancer, attempts at p53 replacement are a logical approach to therapy in this disease. In a phase I study, administration of an adenoviral p53 vector (Adp53) to 21 patients with advanced non-small cell lung cancer produced little toxicity. Up to six intratumoral injections at monthly intervals were well-tolerated. Expression of the p53 transgene was evident, along with potentially useful clinical responses. Time to disease progression in the indicator lesion treated with Adp53 appears to be enhanced by higher doses of vector, concomitant cisplatin therapy, and evidence of apoptosis on tumor biopsy specimens. Phase II trials should now be undertaken to determine the response rate to Adp53.

MeSH Terms (9)

Adenoviridae Antibodies, Viral Carcinoma, Non-Small-Cell Lung Genes, p53 Genetic Therapy Genetic Vectors Gene Transfer Techniques Humans Lung Neoplasms

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