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Spotlight - AG Zuckermann

Combining c-MET inhibition with radiation is effective in MET-fusion driven high-grade glioma

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.

 

Team members
  • Tuyu Zheng (PhD student, co-supervised with Kristian Patjler)
  • Kati Ernst (PhD student, co-supervised with David Jones)
  • Chun Ho Chan (PhD student)
  • Laura von Soosten (PhD student, co-supervised with David Jones)
  • Nina Hofmann (technician)
  • Alessia Cais (PhD student)
  • Marta Cook (MD student)
  • Eric Konrath (animal caretaker)
  • Chiara Lukasch (technical assistant, co-supervised with Lena Kutscher)