Oblimersen
Encyclopedia
Oblimersen 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.
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.
These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004
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.
Antisense therapy
Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...
oligodeoxyribonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
being studied as a possible treatment for several types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, including chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
, B-cell lymphoma
B-cell lymphoma
The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph glands. They develop more frequently in older adults and in immunocompromised individuals ....
, and breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. It may kill cancer cells by blocking the production of Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
—a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that makes cancer cells live longer—and by making them more sensitive to chemotherapy.
History
An antisense oligonucleotideOligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
drug Genasense (G3139) has been developed by Genta Incorporated
Genta (company)
Genta Inc. is a biopharmaceutical company based in Berkeley Heights, New Jersey, United States, which develops products for the treatment of patients with cancer.Its products include:*Genasense...
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
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
(with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.
These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004
By the first quarter 2010, Genasense had not received FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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.
External links
- Augmerosen entry in the public domain NCI Dictionary of Cancer Terms