Yale SPORE in Lung Cancer: The biology and personalized treatment of lung cancer

Nearly 90% of lung cancers worldwide are non-small cell lung cancer (NSCLC) cases, which are largely incurable once they become metastatic. While most cases are linked to smoking, experts are increasingly identifying mutations in light smokers and never-smokers that are treatable.

“The only way to approach a problem as big as lung cancer is to have experts in basic, translational, and clinical research working on several fronts taking the research from the lab to the clinic and back again to develop even newer insights,” said Dr. Herbst. "This effort represents tremendous teamwork by investigators to combat this very common and all-too-fatal disease.”

The Specialized Programs of Research Excellence (SPORE) in Lung Cancer grant was first awarded to Yale in 2015 and renewed in 2020, and supports multidisciplinary research that extends from the laboratory bench to cancer patients in need. Dr. Roy Herbst, Chief of Medical Oncology at Smilow Cancer Hospital and Yale Cancer Center, is the principal investigator of the multi-faceted project. The Yale SPORE conducts projects in immunotherapy, precision medicine, and drug development. Teams will also work to identify new translational research avenues, and train young physician-researchers for careers in lung cancer.

Yale is one of five institutions in the country with a SPORE devoted to lung cancer and one of 12 institutions to house more than one SPORE. The other programs at Yale focus on skin cancer and head and neck cancers.

The Biology and Personalized Treatment of Primary and Metastatic Lung Cancer: The YSILC unites translational scientists spanning diverse areas of cancer research to converge on addressing the challenge of lung cancer. The goal of the YSILC is to reduce mortality from lung cancer through development of novel therapeutics and treatment approaches that are based on an understanding of 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: Test the hypotheses that Siglec-15 (S15) is a major immune suppressor in PD-L1/B7-H1-null lung cancer and that blockade of S15 can be efficacious for a subset of lung cancer patients; Project 2: Evaluate mechanism-based approaches to counter tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer; Project 3: Targeting lung cancer metastasis and drug resistance in the central nervous system. There are three Cores (Administrative; Biostatistics and Bioinformatics; and Biospecimen, Pathology, and Genomics) to support the projects and their clinical aims, mechanistic studies, and evaluation of biomarkers for clinical application. The YSILC also includes strong Developmental Research and Career Enhancement Programs (DRP, CEP) with a history of choosing diverse and productive projects with good outcomes.

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 (either investigator-initiated or NCI-based) 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 agent discovered during our current SPORE research; (2) an improved understanding of genetic and epigenetic mechanisms of resistance to EGFR therapies and how to combat it; (3) an understanding of the mechanism underlying brain metastasis; (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 on lung cancer through our CEP and DRP programs.