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PubMed · 15627020

Bcl-2 antisense therapy in hematologic malignancies.

Asher Chanan-Khan
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Abstract

PURPOSE OF REVIEW: Overexpression of the Bcl-2 oncoprotein is noted in various malignant disorders. In patients with hematologic malignancies, increased production of the Bcl-2 oncoprotein is associated with chemotherapy resistance, aggressive clinical course, and poor survival. Bcl-2 is an important molecular target. Downregulating Bcl-2 can potentially reverse inherent tumor resistance to, and possibly improve response to therapy. This review focuses on the preclinical data, as well as the current clinical information available on oblimersen, a novel antisense approach targeting Bcl-2 in malignant hematologic disorders. RECENT FINDINGS: Early clinical trials have shown single-agent activity of oblimersen in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma, and thus, provide proof of principle for antisense therapy. Phase I and phase II studies using oblimersen in combination with conventional chemotherapy have shown encouraging results in patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute myeloid leukemia. Phase III studies in patients with multiple myeloma and chronic lymphocytic leukemia have completed accrual and results are awaited. SUMMARY: Bcl-2 is a clinically meaningful target in patients with hematologic malignancies. Downregulation of the Bcl-2 oncoprotein can be achieved with oblimersen (antisense molecule specific for Bcl-2). Early clinical results suggest a possible role of this antisense approach in targeting Bcl-2. Ongoing clinical trials will establish the clinical utility of oblimersen in patients with hematologic malignancies.

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Antineoplastic AgentsClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicHematologic NeoplasmsHumansOligonucleotides, AntisenseProto-Oncogene Proteins c-bcl-2Journal ArticleReview

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BibTeXRIS

Asher Chanan-Khan. 2004. Bcl-2 antisense therapy in hematologic malignancies.. https://doi.org/10.1097/01.cco.0000142074.67968.eb

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