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IDrugs. 2009 Jul;12(7):445-53.

Trabedersen, a TGFbeta2-specific antisense oligonucleotide for the treatment of malignant gliomas and other tumors overexpressing TGFbeta2.

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Laval University Hospital Research Center, Department of Endocrinology and Genomics, Quebec City, Canada.


Trabedersen (AP-12009), which is being developed by Antisense Pharma GmbH, is a synthetic antisense oligodeoxynucleotide designed to block the production of TGFbeta2, a secreted protein that can exert protumor effects. Trabedersen is indicated for the treatment of malignant brain tumors and other solid tumors overexpressing TGFbeta2, such as those of the skin, pancreas and colon. Preclinical studies demonstrated that trabedersen reduced the secretion of TGFbeta2 in cultured tumor cells and exhibited antitumor activity ex vivo. It was also demonstrated that chronic intracerebral or intravascular administration of trabedersen did not cause life-threatening side effects in animals. This observation was confirmed in early clinical trials in patients with advanced cancer. In a phase IIb trial, improved survival was observed in patients with brain tumors who were intratumorally administered trabedersen, compared with patients receiving standard chemotherapy. However, this observation requires validation by an ongoing large-scale, phase III, randomized, controlled trial. Meanwhile, continued research on trabedersen should help to determine the roles of TGFbeta2 in cancer and also further the development of antisense technology.

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