Novel models generated by in utero electroporation
Using in utero electroporation we generated a comprehensive range of immunocompetent mouse models for pHGG, including three novel models driven by MET activation. Tumours form these mice can be allografted into immunocompetent animals of the same strain, forming a faithful basis for preclinical trials.
Combining capmatinib + RT increases survival rate and -time in vivo
Using these models, we conducted a preclinical study comparing combinations of MET inhibitors with RT to single treatments. We found that the combination of capmatinib and RT greatly outperformed all other tested therapies, both in terms of survival rate and -time.
Capmatinib pre-treatment induces elevated RT-mediated DNA damage in vitro
By investigating the cellular basis for capmatinib’s synergistic efficacy with RT, we found that the compound increases the amount and persistence of DNA double strand breaks induced by radiation. Further experiments looking into the molecular mechanisms behind this radiosensitization are currently being conducted.
