Since June of 2018, Geert Vandeweyer has managed all the stresses that partners of ROS1 lung cancer take on – supporting his wife Valérie through a year of Crizotinib treatment before her progression and movement to Loratinib in August of 2019. Being a husband, a ROS1der volunteer and father of two is a heavy lift for anyone.
But Geert is about to add “ROS1 cancer researcher” to his caretaking roles. In early December, Geert was awarded a 2280380€ grant from the Flemish Kom op tegen kanker (Stand Up to Cancer) organization. With this funding, granted to the University of Antwerp where he works, Geert will use his expertise as a medical genetics and bio-informatics researcher to manage an ambitious project that aims to accelerate the study of resistance to TKIs among ROS1 patients.
About the study
The study will start from cell lines acquired from the University of Colorado. These are cell lines created from fluid and tumor samples donated by ROS1ders across the U.S. Geert’s team will use these cell lines to test the hypothesis that modern genome engineering techniques like CRISPR/Cas9 can be used to replicate resistance mutations that are seen in real patients into existing cancer models. If Geert’s team can engineer representative cell models, those models would accelerate researchers’ ability to study drug responses when ROS1ders progress, without the need for successful donations to the ROS1 cancer model project.
Second, they hypothesize that the response of drugs against specific resistance mutations, like the G2032R mutation, can be modeled using computer simulations. “Research on EGFR has already proven that one can model how effective binding of TKIs is to various types of progression mutations,” says Geert. “By generating three dimensional models of the ROS1 protein, we hope to achieve the same accuracy for ROS1+ lung cancer. With such a model, we hope to be able to test more TKIs against more types of ROS1 progression mutations.
The grant will fund two technicians at the University of Antwerp for two years, and will cover the cost of experiments. One technician will conduct the cell line work while the other does the computer simulations.
What the research will learn
If the team’s hypothesis is correct, the two year project can provide valuable knowledge. The project hopes to learn: 1. If there are differences in response to targeted therapy drugs (TKIs) between cell lines derived from patients and those generated by the CRISPR process. 2. Which ROS1 TKIs are effective to which resistance mutations. Currently, there is some knowledge about targets for G2032R, but other mutations are less clear. 3. Whether other drugs that are designed for ALK or even TRK might be effective against ROS1 progression mutations.
Ultimately, this knowledge could add models that researchers can use to study ROS1 progression, and offer clinicians more tools as they struggle to make good decisions about treating ROS1 progression.
“Up to now, my research has supervised CRISPR/Cas9 projects that focus on neuronal stem cell modification. I have been studying disorders like autism and intellectual disability,” says Geert. “In order to turn my knowledge to cancer research, I have formed a collaboration with genetics group of the Center for Oncological Research headed by Prof. Guy Van Camp. Also, one of the pathologists at the University Hospital of Antwerp, Prof. Patrick Pauwels, has a long standing interested in ROS1 mutations and nonsmall lung cancer. He will be closely involved.”
Geert has been active in the ROS1 leadership team since late 2018, and the leadership team is thrilled that Geert is taking his involvement to this next level.
“We are all doing the best we can as caregivers,” says Geert. “Because I happen to be involved in genetic and oncology research, I wouldn’t feel comfortable if I didn't try to push our University towards ROS1 research.”