Experimental therapy

Besides analyzing the efficacy of new and promising inhibitors in vivo, we are investigating an experimental therapy approach. Within this project, we are combining selected adeno-associated virus (AAV) variants with oncogene-specific CRISPR-nucleases to treat orthotopic in vivo models. We could identify novel tumor-specific AAV variants as well as oncogene-specific CRISPR-nucleases and are currently combining most promising candidates to evaluate their antitumor efficacy.

Overcoming resistance

In clinical trials, single agent modalities against various targets have displayed potent initial response, yet acquired resistance and tumor relapse is often inevitable. This holds true for many preclinical studies, also when using promising, modern inhibitors. Thus, we are currently aiming at generating resistant tumors in vivo in order to analyze the underlying resistance mechanisms. These efforts will not only provide valuable insight into tumor evolution under treatment but also inform future combinatorial therapy approaches.

Combination therapies

One recently emerged focus of the group is the combination of targeted treatment with radiotherapy (RT). We identified that combining MET inhibition with radiation is highly effective for the treatment of MET-driven pediatric high-grade glioma (pHGG) in multiple preclinical models, greatly outperforming single therapies. We are currently expanding this concept to further pHGG entities.