Exploiting RAD54B-deficiency in colorectal cancer cells through synthetic lethal targeting of PARP1

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McAndrew, Erin N.
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Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in Canada each year. Currently, most therapeutic approaches target rapidly dividing cancer cells by inhibition of normal cellular processes, however these therapies are not selective for cancer cells and unwanted side effects occur. Accordingly, novel cancer-targeted therapeutic strategies and drug targets are urgently needed to diminish the morbidity and mortality rates associated with CRC. Synthetic lethality is a new therapeutic approach that is designed to better target and kill cancer cells by exploiting a cancer-associated mutation (i.e. RAD54B-deficiency) thereby minimizing adverse side effects. We hypothesize that RAD54B-deficient CRC cells will be selectively killed via a synthetic lethal (SL) interaction with PARP1. We have identified and validated a novel drug target, PARP1, within CRC cells harboring RAD54B-deficiencies through a SL paradigm. This study represents the first steps necessary to identify and develop precision medicine based therapeutic strategies to combat CRC.
colorectal cancer, Synthetic lethal, RAD54B, Precision medicine, PARP1