Exploiting Securin Overexpression For Cancer Treatment

Tumour heterogeneity is a major hurdle in the killing of cancer cells, something that we are hoping to overcome through identifying key mutations across cancer cells. We believe one of these key mutated genes to be Securin, a gene involved in regulation of the cell cycle. We are aiming to target Securin through synthetic dosage lethality (SDL,) where the inhibition of one gene in combination with the upregulation of another causes cell death. This project aims to identify genes that are synthetically dosage lethal with Securin through a pooled screen occurring in 2D tissue culture, in-vivo, and in organoids. Pending the results of genetic sequencing, we anticipate that each of the pooled screens will yield overlapping results and give us a few top hits to be investigated further for synthetic dosage lethaltiy, and subsequently for mechanism and drug targetability. We are also hoping that the results of the pooled screen will show organoids and 2D tissue culture to be an appropriate substitute for mice in some situations.