Oblimersen

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Oblimersen
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Oblimersen (INN, trade name Genasense; also known as Augmerosen and bcl-2 antisense oligodeoxynucleotide G3139) is an antisense oligodeoxyribonucleotide being studied as a possible treatment for several types of cancer, including chronic lymphocytic leukemia, B-cell lymphoma, and breast cancer. It may kill cancer cells by blocking the production of Bcl-2—a protein that makes cancer cells live longer—and by making them more sensitive to chemotherapy.

History

An antisense oligonucleotide drug Genasense (G3139) has been developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.

It was shown that the proliferation of human lymphoma cells (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.[1]

These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004.[2]

By the first quarter 2010, Genasense had not received FDA approval due to disappointing results in a melanoma trial. Although safety and efficacy of Genasense have not been established for any use, Genta Incorporated still claims on its website that studies are currently underway to examine the potential role of Genasense in a variety of clinical indications.

References

  1. Dias N, Stein CA (November 2002). "Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". Eur J Pharm Biopharm. 54 (3): 263–9. PMID 12445555. doi:10.1016/S0939-6411(02)00060-7. 
  2. Mavromatis BH, Cheson BD (June 2004). "Novel therapies for chronic lymphocytic leukemia". Blood Rev. 18 (2): 137–48. PMID 15010151. doi:10.1016/S0268-960X(03)00039-0. 

External links

  • Augmerosen entry in the public domain NCI Dictionary of Cancer Terms

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