Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications
Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications
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DOI：
10.1023/a:1024164700094
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发表时间：
2003-08-01
期刊：
影响因子：
7.2
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Chauhan, D;Anderson, KC
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，尽管有所有可用的治疗方法，但仍具有致死性。常规药物的初始治疗有效诱导MM细胞死亡/凋亡;然而，长期药物暴露导致从头化疗耐药性的发展。由于MM是一种骨髓（BM）癌症，疾病的进展和药物疗效受到BM微环境的高度影响。新型药物，如蛋白酶体抑制剂（PS-341）、2-甲氧基乙烯（2 ME 2）、沙利度胺及其免疫调节衍生物（IMiD）和组蛋白脱乙酰酶（HDAC）抑制剂靶向BM微环境中的MM细胞;从而增强抗MM活性并预防耐药性的发展。现在正在描绘介导MM细胞中这些反应的转录事件和信号传导途径，并且可以用于基于中断MM细胞生长或触发MM细胞死亡来鉴定新的治疗靶点。
Multiple myeloma (MM), a hematologic malignancy, remains fatal despite all available therapies. Initial treatment with conventional drugs effectively induces MM cell death/apoptosis; however, prolonged drug exposures results in the development of de novo chemoresistance. Because MM is a bone marrow ( BM) cancer, the progression of disease and drug efficacy is highly influenced by the BM microenvironment. Novel agents, such as proteasome inhibitors (PS-341), 2-methoxyestradiol (2ME2), thalidomide and its immunomodulatory derivatives (IMiDs), and histone deacetylase ( HDAC) inhibitors target the MM cell in its BM microenvironment; thereby enhancing anti-MM activity as well as preventing development of drug-resistance. The transcriptional events and signaling pathways, which mediate these responses in MM cells are now being delineated, and may serve to identify novel therapeutic targets based upon interrupting MM cell growth or triggering MM cell death.