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

M Sasaki, H Ogiwara - Cancer science, 2020 - Wiley Online Library
M Sasaki, H Ogiwara
Cancer science, 2020Wiley Online Library
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 …
Abstract
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.
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