Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities.

Mammalian SWI/SNF complexes in cancer: emerging therapeutic opportunities.
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癌症中的哺乳动物SWI/SNF复合物:新兴的治疗机会。

DOI:
10.1016/j.gde.2017.02.004
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发表时间:
2017-03
影响因子:
4
通讯作者:
Kadoch C
Kadoch C
中科院分区:
生物学2区
文献类型:
--
作者:
St Pierre R;Kadoch C

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哺乳动物SWI/SNF (BAF)染色质重塑复合体协调了一系列影响转录输出的染色质改变。最近的全外显子组测序工作表明,编码mSWI/SNF复合物亚基的基因在超过20%的癌症中发生突变,跨越了广泛的组织类型。大多数突变导致亚基蛋白表达缺失,暗示mSWI/SNF亚基是肿瘤抑制因子。由于缺乏针对由mSWI/SNF亚基扰动产生的复合物或独特途径依赖性的有效和选择性药物,mSWI/SNF缺陷型癌症仍然是一个治疗挑战。在这里,我们回顾了目前由mSWI/SNF复合扰动驱动的人类恶性肿瘤的机制见解和新出现的治疗机会。
Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations. Here, we review the current landscape of mechanistic insights and emerging therapeutic opportunities for human malignancies driven by mSWI/SNF complex perturbation.
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