KRAS-Mutant Mouse Models
Mice are a common and invaluable component of successful scientific research. They have contributed significantly to our understanding of cancer and in the development of cancer treatments. Using mice in an ethically approved, responsible way allows researchers to model the development, progression, and treatment of KRAS-mutant non-small cell lung cancer.
A major goal of the Dream Team is to understand what effects targeted therapies have on the immune system. The Dream Team proposes to use many different mouse model systems in order to fully answer this question. A few of them are outlined below.
- In genetically engineered mouse models (GEMMs), the KRAS gene has been modified to carry the cancer-causing mutation (ex. G12C) that causes KRAS mutant tumors to develop in the lung. These mice can be treated with targeted therapies and the tumor growth or shrinkage can be monitored by magnetic resonance imaging (MRI).
- In a patient-derived xenograft (PDX) model, a small portion of a patient’s tumor can be implanted directly into a mouse. An advantage to using PDX models when studying the effects of anti-cancer drugs is that any tumor regressions seen in the mouse will often occur as well in the patient who provided the tumor sample.
- Humanized mouse models are particularly useful when studying the effects of targeted therapies on the immune system. These mice have had elements of their own immune system (such as T cells) removed and replaced with those of a human immune system.
Researchers on the Dream Team will use all three mouse models to study the novel approach of combining targeted therapies with immunotherapies to assess the effectiveness of this combination at shrinking lung cancer tumors. The results of these preclinical studies will allow the most efficacious treatment strategies to move forward into clinical trials.