Oblimersen Bcl-2 Antisense: Facilitating Apoptosis in Anticancer Treatment
| Autor: | Amanda M. Gillum, Richard J. Klasa, Stanley R. Frankel, Robert E. Klem |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
government.form_of_government
Chronic lymphocytic leukemia medicine.medical_treatment Antineoplastic Agents Apoptosis Pharmacology Biology Genetics medicine Humans RNA Messenger Antisense therapy Base Sequence Oblimersen Melanoma Myeloid leukemia Oligonucleotides Antisense medicine.disease Lymphoma Radiation therapy Proto-Oncogene Proteins c-bcl-2 Cancer research government Chronic myelogenous leukemia medicine.drug |
| Zdroj: | Antisense and Nucleic Acid Drug Development. 12:193-213 |
| ISSN: | 1087-2906 |
| DOI: | 10.1089/108729002760220798 |
| Popis: | The components of the apoptotic program are targets for anticancer therapy. Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies (mAb). Oblimersen sodium (G3139, Genasense, Genta Inc., Berkeley Heights, NJ) is an antisense oligonucleotide (AS-ON) compound designed to specifically bind to the first 6 codons of the human bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and subsequent decrease in Bcl-2 protein translation. Oblimersen is the first oligonucleotide to demonstrate proof of principle of an antisense effect in human tumors by the documented downregulation of the target Bcl-2 protein. A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors. Randomized clinical trials are currently underway to evaluate the efficacy and tolerability of oblimersen in combination with cytotoxic chemotherapy in chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and non-small cell lung cancer. In addition, nonrandomized trials are under way to evaluate oblimersen in non-Hodgkin's lymphoma, acute myeloid leukemia, and hormone-refractory prostate cancer. Preclinical data also support the clinical evaluation of oblimersen in additional tumor types, including chronic myelogenous leukemia and breast, small cell lung, gastric, colon, bladder, and Merkel cell cancers. Enhancement of the efficacy of anticancer treatments with oblimersen Bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy, and ongoing clinical trials will test this therapeutic approach. |
| Databáze: | OpenAIRE |
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