Vanderbilt Molecular and Cellular Characterization Laboratory (Lung)

We will be able to build integrated models of ADC behavior, validate a new genomic molecular test on circulating DNA and propose prospective studies that would eventually offer a different intervention based on these predictions i.e. surgery, vs no surgery, adjuvant immuno- or chemotherapy vs no adjuvant therapy and therefore reduce overtreatment and ultimately increase the rate of cure and reduce healthcare cost.
Aim 1: Assemble and curate: a) a database of screen-detected lung adenocarcinomas from well annotated, publically available studies of screening low dose CT (LDCT) examinations from ongoing and future lung cancer screening trials and centers using standardized acquisition parameters and clinical data elements to define clinical, structural imaging, cellular and molecular attributes of screen detected non-solid, part-solid and solid malignant nodules; b) a database of non-screen detected lung adenocarcinomas from multiple institutions following the same biological attributes. Aim 2: Validate and integrate the structural imaging, genomic tumor DNA analysis and circulating proteomic alterations on a carefully annotated set of early lung adenocarcinomas from Aim 1. Aim 3: Characterize the cellular and molecular heterogeneity of surgically resected screening detected lung nodules using a combination of single cell analysis (CyTOF), genomic analysis of screening detected lung adenocarcinomas. We will identify a minimal set of phenotypic biomarkers that defines inter-tumor and intra-tumor heterogeneity. Aim 4: Develop a novel integrated lung adenocarcinoma prognostic model targeting screen detected adenocarcinomas, building from existing models to incorporate epidemiological, cellular, molecular, and quantitative image analysis.
Suspicious screening-detected lung nodules present a formidable challenge to patients and their providers. The standard of care lacks accuracy in predicting a) malignancy from benign disease and b) indolent vs aggressive behavior. The answer to these questions justifies diametrically opposed strategies (biopsy vs follow up) each of which carries huge consequences including cure of the cancer, risk of death during a procedure or risk of dying from not intervening early in the disease. This application will focus on the behavior of early stage adenocarcinoma of the lung and not on the distinction between benign from malignant nodules. We assembled a unique multidisciplinary group of experts to tackle this problem in an original way. We will develop a retrospective and a prospective repository for both tissue (ADC fresh frozen tissues, blood) and images from which we will derive detailed quantitative structural imaging analysis, targeted genomic analysis and single cell analysis to interrogate the functional genomics of these tumors. The integration of this multidimensional data imaging/molecular/cellular/epidemiology will allow us to identify and validate cellular and molecular determinants of tumor behavior in the context of their inter- and intra-tumor heterogeneity. With these results, we will be able to build integrated models of ADC behavior, validate a new genomic molecular test on circulating DNA and propose prospective studies that would eventually offer a different intervention based on these predictions i.e. surgery, vs no surgery, adjuvant immuno- or chemotherapy vs no adjuvant therapy and therefore reduce overtreatment and ultimately increase the rate of cure and reduce healthcare cost.