Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung Cancer

The Biology and Personalized Treatment of Primary and Metastatic Lung Cancer: The Yale SPORE in Lung Cancer (YSILC) unites translational scientists spanning diverse areas of cancer research to address the challenge of lung cancer. The goal of the YSILC is to increase survival in patients with lung cancer through development of novel therapeutics and treatment approaches that are based on an understanding of the targetable biochemical and immunological pathways involved in progression of lung cancer, acquisition of resistance, and development of metastasis. The YSILC translational research team will accomplish this objective through three projects: Project 1: To explore the role of tumor PLA2G10 upregulation as a dominant mechanism of adaptive immune resistance in NSCLC; Project 2: To optimize precision medicine approaches to treat mutant EGFR-driven lung cancer; Project 3: To target the ATM pathway in treatment-refractory NSCLC patients with brain metastasis. There are three Cores (Administrative; Biostatistics and Bioinformatics; and Biospecimen and Biomarker) to support the projects and their clinical aims, mechanistic studies, and evaluation of biomarkers for clinical application. Strong Developmental Research and Career Enhancement Programs (DRP, CEP) with a robust history of choosing diverse and productive projects with good outcomes are also proposed. The highly coordinated YSILC projects, cores, and programs are focused on developing novel lung cancer therapies with analysis of patient samples, cell-based assays, production of human cell lines and animal models of disease as a guide to design prospective trials that translate these innovative targeted approaches to clinical therapies. Each of these projects has a clinical trial designed to test the sensitivity and resistance of the new therapy with molecular correlates. The expected translational outcomes of the program include: (1) a highly coordinated and focused development of a novel immune target discovered during our current SPORE research; (2) knowledge of new vulnerabilities of EGFR mutant lung cancer that can delay the emergence of drug resistance; (3) an understanding of the mechanism underlying brain metastasis and its treatment; (4) expanding the breadth of lung cancer research by developing the next generation of investigators and encouraging established investigators in other fields to pursue studies in lung cancer through our CEP and DRP programs and to foster a culture of multidisciplinary knowledge within and outside YSILC.