The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Oblimersen Bcl-2 Antisense: Facilitating Apoptosis in Anticancer Treatment
Abstract
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.
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Cites
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Cited by
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B. A., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,416
Bennett, C. F., & Swayze, E. E. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,374
VDAC, a multi-functional mitochondrial protein regulating cell life and death
Shoshan-Barmatz, V., De Pinto, V., Zweckstetter, M., Raviv, Z., Keinan, N., & Arbel, N. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.03.002 · Cited by 782
Bedikian, A. Y., Millward, M., Pehamberger, H., Conry, R., Gore, M., Trefzer, U., Pavlick, A. C., DeConti, R., Hersh, E. M., Hersey, P., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.0483 · Cited by 600
Mustafa, M., Ahmad, R., Tantry, I. Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Moinuddin, Hassan, M. I., Habib, S., et al. (2024) · Cells · doi:10.3390/cells13221838 · Cited by 595
Metadata
- Authors
- Klasa, R. J., Gillum, A. M., Klem, R. E., & Frankel, S. R.
- Venue
- Antisense and Nucleic Acid Drug Development
- Publisher
- SAGE Publications
- Published
- 2002-06
- Volume
- 12
- Issue
- 3
- Pages
- 193-213
- ISSN
- 1087-2906 (ISSN-L)
- OpenAlex
- W1966035396
- Cited by
- 280
- References
- 74
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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