Inhibition of a Selective SWI/SNF Function Synergizes with ATR Inhibitors in Cancer Cell Killing
| Autor: | Gerald R. Crabtree, Jacob G. Kirkland, Vincent D. D’Andrea, Emma J. Chory, Sai Gourinsankar, Emily C. Dykhuizen, Chiung-Ying Chang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Cell type Chemistry Cancer Synthetic lethality medicine.disease Small molecule SWI/SNF 3. Good health Chromatin Cell biology 03 medical and health sciences 0302 clinical medicine Cancer cell medicine biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Function (biology) 030304 developmental biology |
| DOI: | 10.1101/660456 |
| Popis: | SWI/SNF (BAF) complexes are a diverse family of ATP-dependent chromatin remodelers produced by combinatorial assembly that are mutated in and thought to contribute to 20% of human cancers and a large number of neurologic diseases. The gene-activating functions of BAF complexes are essential for viability of many cell types, limiting the development of small molecule inhibitors. To circumvent the potential toxicity of SWI/SNF inhibition, we identified small molecules that inhibit the specific repressive function of these complexes but are relatively non-toxic and importantly synergize with ATR inhibitors in killing cancer cells. Our studies suggest an avenue for therapeutic enhancement of ATR/ATM inhibition and provide evidence for chemical synthetic lethality of BAF complexes as a therapeutic strategy in cancer. |
| Databáze: | OpenAIRE |
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