Gene medicine for cancer treatment: Commercially available …

Drug Des Devel Ther. 2008; 2: 115122.

Published online Feb 6, 2009.

1 Division of Pathology, Chiba Cancer Center Research Institute

2 Division of Gastroenterological Surgery, Chiba Cancer Center, Chiba, Japan

3 Department of Environmental Biochemistry

4 Department of Diagnostic Pathology

5 Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan

Loss of p53 function compromises genetic homeostasis, which induces deregulated DNA replication, damages DNA, and subsequently results in increased resistance to anticancer agents. Pharmacological approaches using recombinant adenoviruses (Ad) have been developed to restore the p53 functions. Another approach for gene medicine is to modify Ad replication in a tumor-specific manner, which induces tumor cell death without damaging normal tissues in the vicinity. The Ad-derived gene medicines, Ad expressing the wild-type p53 gene and replication-competent Ad defective of the E1B-55kDa gene, have been tested for their clinical feasibility and became commercially available in China. These agents demonstrated their antitumor activities as a monotherapy and in combination with conventional chemotherapeutic agents. In this article, we summarize the outcomes of clinical trials in China, most of which have been published in domestic Chinese journals, and discuss potential directions of cancer gene therapy with these agents.

Keywords: gene therapy, cancer, clinical trials, p53, adenovirus, E1B

Cancer is currently one of the main causes of death in Western and Asian societies. Treatments for advanced-stage cancer are often difficult with a limited efficacy despite multimodal therapeutic strategies. Novel approaches are required to improve the prognosis. A molecular targeting with small-sized synthetic chemicals in a certain type of cancer is currently available and furthermore many candidate molecules are under investigation. Gene therapy is also a possible treatment modality and over the past decades has been investigated preclinically and clinically for their feasibility. According to data published in the Journal of Gene Medicine, there have been 1309 approved clinical trials in the world until July 2007 and 66.5% of the trials targeted cancer. Historically, a number of clinical trials have been conducted in the Western world but none of the gene medicines have yet been approved by governmental authorities for commercialization. In contrast, adenoviruses (Ad) expressing the human wild-type p53 gene and Ad defective of the E1B-55 kDa molecule, both of which were originally developed and clinically examined for the efficacy in USA, have been admitted in China. The Ad agents have become the first commercially available gene medicine in the world.

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Gene medicine for cancer treatment: Commercially available ...