Lung Cancer/ Mesothelioma
Research in lung cancer and mesothelioma focuses on understanding the chemoresistance of these resistant thoracic solid tumors. The work concentrates on studies of 3D spheroids, either generated from tumor cell lines or from actual tumor grown ex vivo. With 3D spheroids, tumor cells exhibit additional chemoresistance that mimicks that of solid tumors. The resistance to apoptosis is mediated by altered expression of the Bcl-2 family of anti- and pro-apoptotic proteins within spheroids.
Role of histone deacetylase inhibitors (HDACi) in undermining multicellular resistance of mesothelioma spheroids by altering Bim and Noxa expression.
Use of small molecule molecules to displace Bim from Bcl-2 storage sites and thereby enhance apoptotic response of 3D spheroids to therapeutic agents.
Analysis of changes in genetic expression in cells in 2D compared to 3D for identifying key 3D genetic targets coupled with the use of connectivity analysis to select non-patented drugs that will suppress gene expression of 3D spheroids and thereby reduce resistance.
Testing for pro-apoptotic synergy in human tumor ex vivo spheroids grown from resected viable mesothelioma and lung cancer.
Use of lung cancer pleural effusions to culture lung cancer 3D spheroids for drug screening.