Funding outcome

Annually, one in every four of the 1,600 Canadian women predicted to be diagnosed with cervical cancer will die. The Chan lab has previously shown that a possible treatment that kills cervical cancer cells is the combined inhibition of the Wee1 and Myt1 kinases, proteins that regulate cell division. However, drug resistance during chemotherapy is a major factor to treatment failure, making up 90% of unsuccessful chemotherapies, and must be considered. We have created a cervical cancer cell line that is 20 times more resistant to Myt1 inhibition than its non-resistant parent line. We hypothesize that by comparing gene expression and protein activity between the resistant and non-resistant parent line, we can identify the mechanism behind Myt1 inhibition resistance. We will use a technique called RNA-seq to measure gene expression in each cell line. We will also use a technique called reverse phase protein assays to identify changes in cellular pathways. We will then use technology to analyze the data and rank the most over-expressed and suppressed genes and pathways to identify the key genes/pathways. We believe that overexpression of key genes/pathways in the resistant cell line causes resistance to Myt1 inhibition, allowing cancer cells to survive treatment. Therefore, suppressing these genes/pathways in the resistant line is expected to lower resistance to Myt1 inhibition by 'correcting' the deviation, allowing the treatment to kill cancer cells. We will test this by inducing overexpression in the non-resistant line, knockout in the resistant line, and evaluate cancer cell viability in response to Myt1 inhibition. By identifying the factor(s) responsible for Myt1 inhibition resistance, it can potentially be used to screen patients for Myt1 inhibition. This would lead to more targeted, effective treatments that are less susceptible to resistance and are more likely to be successful, improving the life expectancy of cervical cancer patients.