Pierre P. Massion, MD
Cornelius Vanderbilt Chair in Medicine
Professor, Cornelius Vanderbilt Chair in Medicine
MD - Universite Catholique de Louvain, Belgium
BS - Universite Catholique de Louvaine, Belgium
Lung Tumorigenesis and Early Detection
The laboratory of Dr. Massion emphasis is on lung tumorigenesis and on using molecular approaches to identify markers of lung neoplasia and to test those in multidisciplinary early detection strategies.
1. The Role of chromosome 3q amplification in lung cancer Genomic instability is a key attributes of cell undergoing transformation. Chromosomal alterations are a key feature of malignant transformation. We have established the amplicon develops before the tumor has acquired invasive properties. We identified key contributors to tumorigenesis in this amplicon including PIK3CA, TP63, ECT2, PRKCI and FXR1. We established FXR1 as a novel oncogenic driver and able to work in concert with other genes in the same amplicon. We have established the molecular basis for the role of this amplicon in NSCLC, we identified this genomic alterations as a potential candidate biomarkers of progression among preinvasive lesions and discovered that RNA binding proteins may play a key role in tumor development. 2. Field of cancerization and metabolic alterations. The airway epithelium represents a large field of injury where cells get exposed to carcinogens. Those lead to stochastic DNA alterations which eventually predisposes to tumor formation. We undertook an in depth proteomic and genomic analysis of these alterations in search for determinants of lung cancer progression. We discovered metabolic alterations in high risk individuals and in early lung cancer. We identified genomic and proteomic alterations suggesting of lung cancer progression. We tested these attributes functionally to discover some key molecular determinants of lung cancer progression. 3. Non-invasive evaluation of indeterminate pulmonary nodules (IPNs). The management of IPNs represents one of the most urgent clinical problems arising from lung cancer screening. We are testing whether integrating clinical, advanced imaging and molecular techniques will optimize the diagnostic accuracy for IPNs. We demonstrated proof of concept that deep learning approaches could improve early discrimination of benign from malignant IPNs. This work should revolutionize the field, leading to improved management of IPNs. 4. Tumor heterogeneity in SCLC. Small cell lung cancer is a recalcitrant lung tumor that carries the worst prognosis. There has been no significant in outcome in the last 30 years. We discovered genomic alterations in SCLC that are centered on neuroendocrine biology and cellular differentiation. We characterized new candidate targets in SCLC including FAK and SYK kinases. We have established a basis for potential new therapeutic strategies. More recently we characterized its cellular heterogeneity and identified two phenotypes mesenchymal and neuroendocrine with specific adhesion properties, biomarkers and transcription factor profiles.