Resistance on TKI of mutation+ NSCLC in PDX

If patients are treated with targeted therapy in mutation-positive lung cancer, the tumors will become resistant to the treatment. At progression, we often find new mutations present in the tumor cells, which could be targeted with new treatments. Many cases are discussed in the molecular tumor board, where we use 3D modeling, to predict optimal treatment options. To get better insight of the prediction of this mathematic tool, we will compare outcome of the 3D modeling and cultures of patient derived cells from the patients discussed in the molecular tumor board (MTB), which will be treated with different TKI. On the other hand we often cannot find the mechanism of resistance to TKI treatment. We will also use patient derived cell cultures to search for new mechanisms using for example DNA and RNA sequencing. If we find new mechanisms of resistance we will focus of these aberrations in lung cancer cell lines. In this project the University Medical Centre Groningen collaborates with the Hanze University of Applied Sciences. We have a partnership with different private pharmaceutical companies who are involved in the treatment of lung cancer. 

We expect that this project will help to make progress in the use of personalized medicine in lung cancer and that outcomes of this research can help patients all over the world.  The UMCG will focus on the patient derived cell lines and the 3D-modeling used in the UMCG-MTB. HUAS will focus on lung cancer cell lines. 

At the end of this project we expect that we have optimized our culturing of patient derived cells and that we are able to compare this to 3D-modeling results. We also expect that new found mechanisms can be used in lung cancer cell line research and that we can use this knowledge to find more treatment options after this project. 

This study advances our understanding of resistance mechanisms in targeted therapies for EGFR, ALK, ROS1, and BRAF-positive NSCLC. By integrating patient-derived cell models, genomic analyses, and functional drug screening, we aim to contribute to the development of more effective and durable treatment strategies for patients with NSCLC.