Carla Concepcion, PhD

Advances in lung cancer treatments have improved patient outcomes, but patients still die from the disease. A certain type of lung cancer, which has changes in a specific protein (SMARCA4) is very aggressive, spreads easily and does not have effective therapies. A promising new therapy that targets a different protein (SMARCA2) in these lung cancers is being tested in clinical trials. However, we do not know how these treatments will affect how the tumors grow and change over time, especially since tumors are complex groups of cells that can change and adapt to therapies. In fact, some forms of SMARCA4-altered lung cancer do not respond to this therapy. To study this, we've created animal models that closely mimic the human disease. These models help us understand how this new therapy works and how it affects tumor growth and evolution. By doing this research, we will find ways to make this new therapy even better at fighting tumors for patients that urgently need them.

Update: Over the past year, we have run preclinical studies to understand how a lethal molecular subtype of lung cancer (SMARCA4-deficient lung adenocarcinomas) is able to evade a leading therapeutic strategy (SMARCA2 degradation). We are using genetically engineered mouse models that faithfully phenocopy human disease to study how tumors respond to this therapy and how they overcome it. Our experiments show that cancer cells have variable responses to this therapy. Although all the cancer cells have the same genetic mutations, some cells are better at adapting to this therapy and overcoming it than other cells. These persistent cells are eventually able to grow and spread to other organs. This indicates that there are factors beyond genetic sequence that determine whether cancer cells respond. We are currently investigating what these other factors are. In parallel, we are also investigating a rare, highly aggressive form of lung cancer called SMARCA4 undifferentiated tumors (SMARCA4-UT) and trying to understand why they are so aggressive. To do this, we are using patient samples and building new models to better study the disease. Our long-term goal is to use this knowledge to inform future therapeutic strategies.