Understanding synthetic lethality of ATR inhibitors with DDR dysregulation common in ovarian cancer

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Key words:Living a long and Healthy lifeDNA damage response: DNA repair and cell cycle checkpoints, ATRTranslational studies for Biomarker development Patient stratification to new treatments for ovarian cancerThis project aims to explore the therapeutic potential of an ATR inhibitor, developed at Vertex Pharmaceuticals, in ovarian cancer through exploitation of defects in the DNA damage response (DDR). ATR is key to the DDR by signalling DNA damage to cell cycle checkpoints and repair. Certain defects in the DDR confer sensitivity to ATR inhibition. Many of these defects are common in ovarian cancer, the 5th most frequent cause of cancer death in women. The project will involve cytotoxicity studies in a panel of ovarian cancer cell lines, knockdown of DDR genes, mechanistic studies to determine why some DDR defects confer sensitivity to ATR inhibition and translational studies using primary cultures of ovarian cancer from patients. Training in relevant biochemical and molecular techniques, the scientific method and intellectual rigor will be given. Parts of the project will be undertaken at Vertex, the industrial sponsor's laboratories.