Uncovering kinase inhibitor resistance mechanisms via CRISPR-based gain-of-function mutagenesis.

Drug resistance to is a common problem in anti-cancer and antiviral therapy. Understanding the molecular mechanisms underlying the development of drug resistance is necessary to be able to intervene both preventively and repressively. The research group of Prof. dr. Dirk Daelemans (Laboratory of Virology and Chemotherapy) recently developed a CRISPR-based methodology for detecting such resistance mechanisms via gain-of-function mutagenesis in the direct target protein of drugs. This PhD research will adapt and optimize this methodology to detect resistance mechanisms in proteins beyond the drug target. The focus is mainly on identifying novel mechanisms of kinase inhibitor resistance due to mutations both in- and outside the drug target. We expect our study to provide new knowledge on genes and mutation sites involved in resistance to different kinase inhibitors, in order to uncover biomarkers or new potential targets for counteracting therapy resistance.