2010 UALC
Don Nguyen, PhD
Yale University
Research Project:
Identifying in vivo mechanisms of therapeutic resistance by brain metastasis from lung adenocarcinoma
Summary:
A long-standing clinical observation is that by the time cancers have spread to other organs, they are generally untreatable. In the case of lung cancer, tumors acquire resistance to different forms of therapy while spreading rapidly to the central nervous system. The mechanisms linking these two features remain poorly understood. Dr. Nguyen will be using a mouse model that mimic the clinical and molecular features of lung cancer metastasis to the brain to understand how tumors can gain resistance when interacting with brain tissue.
More Content:
Final Report
Dr. Nguyen has identified a new molecular subset of cells that have properties of poorly differentiated stem cells of the distal airways. Patients with these tumors have increased incidence of metastasis and poor survival rates. Most of the gene expression changes in these tumors can be ascribed to a small set of transcription factors which regulate tumor microenvironment interactions and metastasis, providing clinically relevant targets for future study. Dr. Nguyen’s team has also made significant progress in modeling brain tumor microenvironment interactions in 3D models, and is currently testing the effects on therapeutic resistance to erlotinib and aftinib (two EGFR inhibitors) as well as testing the role of several clinically validated candidate genes. The goal is to identify genes of this molecular tumor subset that mediate both interaction with the brain as well as therapeutic resistance.
Notable Accomplishments
Dr. Nguyen has garnered over $2 million in follow-on funding.