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首页> 外文期刊>Expert opinion on therapeutic targets >Targeting c-Myb expression in human disease.
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Targeting c-Myb expression in human disease.

机译：靶向人类疾病中的c-Myb表达。

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c-Myb is a transcription factor employed in the haematopoietic system and gastrointestinal tract to regulate the exquisite balance between cell division, differentiation and survival. In its absence, these tissues either fail to form, or show aberrant biology. Mice lacking a functional c-myb gene die in utero by day 15 of development. When inappropriately expressed, as is common in leukaemia and epithelial cancers of the breast, colon and gastro-oesophagus, c-Myb appears to activate gene targets of key importance to cancer progression and metastasis. These genes include cyclooxygenase-2 (COX-2), Bcl-2, BclX(L) and c-Myc, which influence diverse processes such as angiogenesis, proliferation and apoptosis. The clinical potential for blocking c-Myb expression in malignancies is based upon strong preclinical data and some trial-based evidence. The modest clinical experience to date has been with haematopoietic malignancies, but other disease classes may be amenable to similar interventions. The frontline agents to achieve this are nuclease-resistant oligodeoxynucleotides (ODNs), which are proving to be acceptable therapeutic reagents in terms of tolerable toxicities and delivery. Nevertheless, further effort must be focused on improving their efficacy, eliminating non-specific toxicity and optimising delivery. Optimisation issues aside, it would appear that anti-c-Myb therapies will be used with most success when combined with other agents, some of which will be established cytotoxic and differentiation-inducing drugs. This review will explore the future strategic use of ODNs in vivo, focusing on a wide spectrum of diseases, including several beyond the haematopoietic malignancies, in which c-Myb appears to play a role.
机译：c-Myb是在造血系统和胃肠道中使用的转录因子，可调节细胞分裂，分化和存活之间的平衡。如果没有，这些组织要么无法形成，要么表现出异常的生物学特性。缺乏功能性c-myb基因的小鼠在发育第15天时在子宫内死亡。如果表达不当（如在白血病和乳腺癌，结肠癌和胃食管上皮癌中常见），c-Myb似乎可以激活对癌症进展和转移至关重要的基因靶标。这些基因包括环氧合酶2（COX-2），Bcl-2，BclX（L）和c-Myc，它们影响多种过程，例如血管生成，增殖和凋亡。阻断c-Myb在恶性肿瘤中表达的临床潜力是基于强大的临床前数据和一些基于试验的证据。迄今为止，仅有少量的临床经验涉及造血系统恶性肿瘤，但其他疾病类别也可能需要进行类似的干预。实现这一目标的第一线药物是耐核酸酶的寡脱氧核苷酸（ODN），就可耐受的毒性和递送而言，事实证明它们是可接受的治疗剂。然而，必须进一步努力集中于提高其功效，消除非特异性毒性和优化递送。除了优化问题之外，似乎将抗c-Myb疗法与其他药物联合使用将获得最大的成功，其中一些药物将被确立为细胞毒性和诱导分化的药物。这篇综述将探讨ODN在体内的未来战略应用，重点关注多种疾病，包括除造血系统恶性肿瘤以外的几种疾病，其中c-Myb似乎发挥了作用。

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