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靶向多发性骨髓瘤中的 MYC。

Targeting MYC in multiple myeloma.

机构信息

IRCL, INSERM UMR-S1172, Univ. Lille, Lille, France.

Institute of Medical Genetics, Univ. Lille, CHU, Lille, France.

出版信息

Leukemia. 2018 Jun;32(6):1295-1306. doi: 10.1038/s41375-018-0036-x. Epub 2018 Feb 22.

Abstract

Multiple myeloma (MM) is a plasma cell tumor marked by clonal evolution and preceded by a premalignant stage, which progresses via molecular pathway deregulation, including MYC activation. This activation relates to translocation or gain of the MYC locus and deregulation of upstream pathways such as IRF4, DIS3/LIN28B/let-7, or MAPK. Precision medicine is an approach to predict more accurately which treatment strategies for a particular disease will work in which groups of patients, in contrast to a "one-size-fits-all" approach. The knowledge of mechanisms responsible for MYC deregulation in MM enables identification of vulnerabilities and therapeutic targets in MYC-driven tumors. MYC can be targeted directly or indirectly, by interacting with several of its functions in cancer. Several such therapeutic strategies are evaluated in clinical trials in MM. In this review, we describe the mechanism of MYC activation in MM, the role of MYC in cancer progression, and the therapeutic options to targeting MYC.

摘要

多发性骨髓瘤(MM)是一种浆细胞瘤,其特征为克隆进化,并伴有恶性前阶段,该阶段通过分子途径失调进展,包括 MYC 激活。这种激活与 MYC 基因座的易位或获得以及上游途径(如 IRF4、DIS3/LIN28B/let-7 或 MAPK)的失调有关。精准医学是一种方法,可以更准确地预测特定疾病的哪些治疗策略将在哪些患者群体中起作用,而不是采用“一刀切”的方法。了解导致 MM 中 MYC 失调的机制,可以确定 MYC 驱动肿瘤中的脆弱性和治疗靶点。MYC 可以通过与癌症中的几个功能相互作用直接或间接靶向。在 MM 的临床试验中评估了几种此类治疗策略。在这篇综述中,我们描述了 MM 中 MYC 激活的机制、MYC 在癌症进展中的作用以及针对 MYC 的治疗选择。

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