Synthetic lethal therapy based on targeting the vulnerability of SWI/SNF chromatin remodeling complex-deficient cancers

被引：41

作者：

Sasaki, Mariko ^{[1
,2
]}

Ogiwara, Hideaki ^{[1
]}

机构：

[1] Natl Canc Ctr, Res Inst, Div Canc Therapeut, Tokyo, Japan

[2] Jikei Univ, Grad Sch Med, Mol Oncol, Tokyo, Japan

来源：

CANCER SCIENCE | 2020年 / 111卷 / 03期

关键词：

chromatin remodeling; epigenetics; molecular targeted therapy; precision medicine; synthetic lethality; MALIGNANT RHABDOID TUMORS; OXIDATIVE STRESS; CELL CARCINOMA; BAF COMPLEXES; CYCLIN D1; INHIBITION; SMARCA4; DNA; CHECKPOINT; EXPRESSION;

D O I：

10.1111/cas.14311

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The SWI/SNF chromatin remodeling complex is composed of approximately 15 subunits, and approximately 20% of all cancers carry mutations in the genes encoding these subunits. Most of the genetic alterations in these genes are loss-of-function mutations. The identification of vulnerability based on synthetic lethality in cancers with SWI/SNF chromatin remodeling complex deficiency contributes to precision medicine. The SWI/SNF chromatin remodeling complex is involved in transcription, DNA repair, DNA replication, and chromosomal segregation. Cancers with deficiency in the SWI/SNF chromatin remodeling complex show increased vulnerability derived from the loss of these functions. Synthetic lethal targets have been identified based on vulnerabilities in the functions of the SWI/SNF chromatin remodeling complex. In this review article, we propose a precision medicine strategy using chemotherapeutic methods, such as molecular targeted therapy and immunotherapy, based on harnessing synthetic lethality in cancers with deficiency in the SWI/SNF chromatin remodeling complex.

引用

页码：774 / 782

页数：9

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