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  • Title: Bcl-2 antisense therapy in multiple myeloma.
    Author: Chanan-Khan AA.
    Journal: Oncology (Williston Park); 2004 Nov; 18(13 Suppl 10):21-4. PubMed ID: 15651173.
    Abstract:
    Most malignant plasma cells overexpress Bcl-2, which contributes to resistance against apoptosis induced by dexamethasone and other anticancer agents. Oblimersen sodium (Genasense, previously known as G3139), an antisense oligonucleotide that specifically binds to bcl-2 messenger RNA, decreases production of Bcl-2 protein in both human myeloma cell lines, as well as in ex vivo purified myeloma cells, and enhances the cytotoxicity of dexamethasone and doxorubicin. Combining oblimersen with other anticancer agents represents a therapy-enhancing strategy to reverse the multidrug resistance seen in multiple myeloma (MM). Phase II trials are evaluating the potential role of oblimersen in reversing resistance to standard therapies. Preliminary results from these trials in patients with refractory or relapsed MM indicate that the combination of oblimersen with dexamethasone/thalidomide (Thalomid) or vincristine/doxorubicin/dexamethasone is active and well tolerated and that oblimersen may help overcome chemotherapy resistance and restore sensitivity to MM cells. A randomized phase III clinical trial comparing dexamethasone plus oblimersen with dexamethasone alone in patients with relapsed or refractory myeloma has completed enrollment, with results expected to be available in 2004. Future studies will focus on the role of oblimersen in combination with novel biologic agents such as bortezomib (Velcade).
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