Development of novel precision cancer therapy based on collateral lethality
We are looking for motivated students that want to develop their skills in laboratory work centered on drug screening in cell and organoid models, or students that want to work with bioinformatic analysis to search for new potential targets to study.
The aims are to identify drug candidates that selectively kill cancer cells that are deficient in a defined enzymatic activity, and determine the mechanism of action for the hits that validate.
Tumors with loss of heterozygosity (LOH) may be sensitized to certain anticancer drugs due to loss of enzyme catalytic activities that exist in normal cells. Through bioinformatic analysis of genomic variants, we have identified an enzyme important for metabolizing and eliminating a large proportion of clinically used drugs as a candidate target for novel cancer drug discovery and development under this concept. We have developed cell models with high or low activity of this enzyme and use these cell lines to screen for known drugs or novel compounds whose cytotoxicity is affected by the enzymatic activity.
In the project we will 1) perform drug library screening to select drug candidates that show greater potency on cells with low enzymatic activity, 2) carry out extended studies of potential hits, and 3) develop effective therapeutic strategies by combining conventional medicines with identified novel hit compounds. Several libraries of known cancer drugs and novel compounds will be investigated. We are therefore looking for students who want to work with wet-lab techniques, such as immunoblotting, cell and organoid culture, and drug screening.
There are also opportunities to work with bioinformatics and/or molecular studies to identify and select new potential targets for this novel therapy concept in adult and pediatric cancers.