Remodeling the cancer epigenome: mutations in the SWI/SNF complex offer new therapeutic opportunities.

Remodeling the cancer epigenome: mutations in the SWI/SNF complex offer new therapeutic opportunities. Expert Rev Anticancer Ther. 2019 Apr 15;: Authors: Orlando KA, Nguyen V, Raab JR, Walhart T, Weissman BE Abstract INTRODUCTION: Cancer genome sequencing studies have discovered mutations in members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex in nearly 25% of human cancers. The SWI/SNF complex, first discovered in S. cerevisiae, shows strong conservation from yeast to Drosophila to mammals, contains approximately 10-12 subunits and regulates nucleosome positioning through the energy generated by its ATPase subunits. The unexpected finding of frequent mutations in the complex has fueled studies to identify the mechanisms that drive tumor development and the accompanying therapeutic vulnerabilities. Areas covered: In the review, we focus upon the potential roles different SWI/SNF subunit mutations play in human oncogenesis, their common and unique mechanisms of transformation and the potential for translating these mechanisms into targeted therapies for SWI/SNF-mutant tumors. Expert opinion: We currently have limited insights into how mutations in different SWI/SNF subunits drive the development of human tumors. Because the SWI/SNF complex participates in a broad range of normal cellular functions, defining specific oncogenic pathways has proved difficult. In addition, therapeutic options for SWI/SNF-mu...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research