Project Details
Description
The occurrence of a chromosomal translocation resulting in a ROS1 gene fusion in lung cancer is relatively rare with around 1-2% of all cases. Both Dutch (Stichting Merels Wereld) and world-wide (ROS1ders) patient advocacy groups work hard to raise awareness and bring researchers together to close the knowledge gap on ROS1 driven oncogenesis and increase the options
for treatment. A notorious hurdle is to achieve durable responses due to development of resistance.
Ongoing mutations occurring in tumour cells lead to a heterogeneous genomic landscape and will result in outgrowth of the fastest growing tumour cell population resistant to the applied drug. The currently known resistance mechanisms can be divided in on-target (i.e. mutations in the kinase
domain of ROS1) and off-target (providing ROS1 independent growth support) mechanisms. The currently available drugs target the ROS1-fusion gene positive lung cancer cells. In addition, some of the drugs also target cancer cells with specific ROS1 resistance mutations allowing effective sequential
treatment upon disease progression. Selection of the most optimal treatment is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction of the most effective follow-up treatment upon development of resistance. Medical Life Science & Diagnostics can help to improve
treatment by developing cell culture models which mimic the situation in resistant tumour cells.
Understanding the impact of specific mutations on disease behaviour will aid in the development of patient-tailored therapeutic approaches, ultimately improving patient outcomes.
for treatment. A notorious hurdle is to achieve durable responses due to development of resistance.
Ongoing mutations occurring in tumour cells lead to a heterogeneous genomic landscape and will result in outgrowth of the fastest growing tumour cell population resistant to the applied drug. The currently known resistance mechanisms can be divided in on-target (i.e. mutations in the kinase
domain of ROS1) and off-target (providing ROS1 independent growth support) mechanisms. The currently available drugs target the ROS1-fusion gene positive lung cancer cells. In addition, some of the drugs also target cancer cells with specific ROS1 resistance mutations allowing effective sequential
treatment upon disease progression. Selection of the most optimal treatment is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction of the most effective follow-up treatment upon development of resistance. Medical Life Science & Diagnostics can help to improve
treatment by developing cell culture models which mimic the situation in resistant tumour cells.
Understanding the impact of specific mutations on disease behaviour will aid in the development of patient-tailored therapeutic approaches, ultimately improving patient outcomes.
Layman's description
How does a specific lung cancer become resistant towards medication.
| Short title | ROS1+ NSCLC |
|---|---|
| Status | Active |
| Effective start/end date | 1/09/24 → 31/08/28 |
Collaborative partners
- Hanze University of Applied Sciences (lead)
- University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology
- University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine