YALE SPORE IN LUNG CANCER (YSILC) OVERALL SUMMARY 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-negative 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. Strong Developmental Research and Career Enhancement Programs (DRP, CEP) with a 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 (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.

Public Health Relevance

OVERALL NARRATIVE Lung cancer is the number one cause of cancer death in the United States and the Yale SPORE in Lung Cancer is designed to identify novel biologic pathways and test new therapeutic approaches to interfere with lung cancer progression and metastasis. All three projects in the SPORE will initiate Yale-led novel clinical trials and will promote bench to bedside research within the center. This program has the potential to make significant impact in guiding the selection of therapies most likely to provide benefit to lung cancer patients with treatment refractory disease in the primary or metastatic setting.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Ujhazy, Peter
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
Zip Code
Burslem, George M; Smith, Blake E; Lai, Ashton C et al. (2018) The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study. Cell Chem Biol 25:67-77.e3
Liu, Huafeng; Li, Xin; Hu, Li et al. (2018) A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma. Cell Mol Immunol 15:838-845
Choe, Junho; Lin, Shuibin; Zhang, Wencai et al. (2018) mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature 561:556-560
Bade, Brett C; Hyer, J Madison; Bevill, Benjamin T et al. (2018) A Patient-Centered Activity Regimen Improves Participation in Physical Activity Interventions in Advanced-Stage Lung Cancer. Integr Cancer Ther 17:921-927
Tentori, Augusto M; Nagarajan, Maxwell B; Kim, Jae Jung et al. (2018) Quantitative and multiplex microRNA assays from unprocessed cells in isolated nanoliter well arrays. Lab Chip 18:2410-2424
Fan, Pang-Dian; Narzisi, Giuseppe; Jayaprakash, Anitha D et al. (2018) YES1 amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics. Proc Natl Acad Sci U S A 115:E6030-E6038
Gupta, Swati; Mani, Navin R; Carvajal-Hausdorf, Daniel E et al. (2018) Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Lab Invest 98:1076-1083
Robichaux, Jacqulyne P; Elamin, Yasir Y; Tan, Zhi et al. (2018) Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med 24:638-646
Bondeson, Daniel P; Smith, Blake E; Burslem, George M et al. (2018) Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead. Cell Chem Biol 25:78-87.e5
O'Malley, Stephanie S; Zweben, Allen; Fucito, Lisa M et al. (2018) Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial. JAMA Psychiatry 75:129-138

Showing the most recent 10 out of 74 publications