Gene medicine for cancer treatment: Commercially available medicine and accumulated clinical data in China
Guangyu Ma1,3, Hideaki Shimada2, Kenzo Hiroshima4, Yuji Tada5, Nobuo Suzuki3, Masatoshi Tagawa1
1Division of Pathology, Chiba Cancer Center Research Institute; 2Division of Gastroenterological Surgery, Chiba Cancer Center, Chiba, Japan; 3Department of Environmental Biochemistry; 4Department of Diagnostic Pathology; 5Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan
Abstract: 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
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