New preclinical model could accelerate thymic cancer research

A new preclinical model of thymic cancer developed by Weill Cornell Medicine researchers has revealed insights into how common mutations found in thymic epithelial tumors trigger their formation. The model could help speed up the development of targeted therapies for cancer of the thymus, a gland that makes immune cells that help protect the body from infection.

In an article published in magazine on August 29 Thoracic Oncology in this study , senior author Giuseppe Giaccone, PhD, Professor of Medicine and Associate Director of Clinical Research, Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College, and colleagues Colleagues describe a genetically engineered mouse model in which the animals’ thymic epithelial cells contain a genetic variant called GTF2I L424H, the most common mutation in thymic cancer.

“Having a mouse model of thymic epithelial tumors will help us learn more about how these tumors form and allow We were able to test new treatments,” said Dr. Giaccone, also an oncologist at New York-Presbyterian/Weill Cornell Medical Center.

The study’s lead author, Dr. Yongfeng He, Lecturer in Cancer Biology at Weill Cornell Medicine, explained that thymic cancer It is a rare, complex and understudied cancer. Certain autoimmune diseases are associated with thymic epithelial tumors, but the cause is unknown. Currently, there are no good preclinical models that can reproduce disease characteristics in humans, and there are only a handful of cell lines to study, he said.

Lack of experimental models hinders research into new treatments for the disease. Surgery is often the treatment of choice, but if that fails, thymic cancer patients may receive chemotherapy, immunotherapy, or other targeted therapies developed for different cancers. However, these second-line therapies are not curative, Dr. Giaccone said.

“We want to understand why these tumors occur and how we can develop curative therapies,” he said. Thymic epithelial cells were mutated and cells were found to develop abnormally in young animals. As animals age, tumors develop in their thymus glands. They found that the expression of many genes involved in the production of new thymocytes was altered in the mice, including genes previously associated with other cancers. When the team compared mouse tumors to human thymic cancer samples, they found that the mouse tumors shared many molecular features with B1 and B2 human thymic tumors.

“We believe that the GTF2I L424H mutation initiates the process of tumor formation,” said Dr. Giaccone. “Adding more mutations may make the tumor more aggressive.”

The next step for the team will be to precisely study this How this mutation arises, causes the thymus to become cancerous and what other genetic pathways are involved, he said. Because the gene affected by the GTF2I L424H mutation controls the expression of many other genes, Dr. Ho said it may not be a good target for anticancer therapy. But some of the other genes it turns on or off could be potential targets.

“We can use our mouse model to test that drugs targeting these other genes can find targets for thymic epithelial tumors. better therapy,” he said.