An approach called synthetic lethality targets biological systems in which two or more genetic pathways interact to contribute to a vital cellular process. The loss of either pathway does not threaten cell viability and may indeed provide a survival advantage, such as the case with cancer cells; however, lethality is observed when both pathways are inhibited, which may be achieved using specific inhibitory compounds. ACRI scientists are working to identify the pathways in cancer cells that can elicit synthetic lethality and develop compounds that can take advantage of these discoveries. These experiments should lead to compounds that target only cancer cells (which already have loss-of-function in one pathway) and have no effect on normal cells, thus avoiding the side effects associated with current therapies.
Using CRISPR-Cas9 technology, ACRI researchers are working to identify pathways in cancer cells that can cause synthetic lethality to enable the development of compounds that can benefit from these discoveries. These experiments should lead to compounds that only target cancer cells (which already have loss of function in a pathway) and which have no effect on normal cells, thus avoiding the side effects associated with current treatments. These same tools are currently used at ACRI for the development of a diagnostic system whose goal is to identify among the drugs currently available, the best candidate for the treatment of patients who would not respond, or have difficulty in conventional treatments.
- Dr Sandra Turcotte
