Rapport final
Improved targeted therapies in non-small cell lung cancer: an unbiased approach to increase treatment efficacy (De Grève Jacques)
We have used an elaborated siRNA screen (kinase and ubiquitin libraries) to discover mechanisms of functional drug tolerance in EGFR mutant lung cancer treated with EGFR inhibitors. One of the prime candidates, among others, resulting from this investigation was USP13. We have then investigated the mechanisms by which USP13 supports tolerance to EGFR targeted therapies in cell lines representing EGFR-mutant non-small cell lung cancer. USP13 achieves this effect by stabilization of the EGFR in these cells. This effect is selective for mutant EGFR compared to wild-type EGFR. Co-targeting of USP13 increases the sensitivity of these cells to EGFR targeted therapies in cell culture experiments and a mouse model. Our study provides a basis for the potential of USP13 targeted therapies for the treatment of EGFR mutated non-small cell lung cancer.