IngentaConnect Bcl-2-Targeted Antisense Therapy (Oblimersen Sodium): Towards Cli...

Authors: Nuno Moreira, Joao¹; Santos, Adriana¹; Simoes, Sergio¹

Source: Reviews on Recent Clinical Trials, Volume 1, Number 3, September 2006 , pp. 217-235(19)

Publisher: Bentham Science Publishers

Abstract:

The identification of activated oncogenes, such as the bcl-2, in several types of cancer has made it possible to consider such genes as targets for antitumor therapy. Bcl-2 is an anti-apoptotic protein, whose overexpression is associated with chemotherapy resistant cancer, aggressive clinical course and poor survival. The development of novel targeted gene-silencing strategies, such as those based on the use of antisense oligonucleotides, represents a renewed hope in the treatment of cancer. Within this scope, this review covers the main pre-clinical aspects and the most recent clinical data obtained with Oblimersen sodium (Genta Inc.). Oblimersen is a 18-mer phosphorothioate antisense oligonucleotide designed to bind to the first six codons of the human bcl-2 mRNA. Phase I/II trials indicate that infusion of Oblimersen provides biologically relevant plasma levels that lead to downregulation of target Bcl-2 protein. Moreover, the use of Oblimersen in combination with chemotherapy in a variety of cancers has shown promising response rates with good tolerability. Randomized phase III trials are currently underway to evaluate whether the combined use of Oblimersen with standard treatment is superior to standard treatment alone in chronic lymphocytic leukaemia, malignant melanoma and multiple myeloma. Overall, the enhanced efficacy of anticancer treatments of this bcl-2-targeted antisense therapy represents a promising new apoptosis-modulating strategy.

Keywords: Cancer therapy; bcl-2 antisense oligonucleotide; Apoptosis; Clinical trials

Document Type: Research article

DOI: 10.2174/157488706778250050

Affiliations: 1: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, and Center for Neuroscience and Cell Biology, University of Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal.

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Bcl-2-Targeted Antisense Therapy (Oblimersen Sodium): Towards Clinical Reality