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

耶鲁 SPORE 肺癌 (YSILC)：肺癌的生物学和个性化治疗

• 批准号: 10203850
• 负责人: Roy S Herbst
• 金额: $ 200.37万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-26 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203850
• 关键词: Address; Adoption; Animal Disease Models; Area; Award; Biochemical; Biochemistry; Bioinformatics; Biological; Biological Assay; Biology; Biometry; Biopsy; Blood; Brain; Brain Neoplasms; Cancer Biology; Cancer Etiology; Cancer Hospital; Cancer Patient; Cell surface; Cells; Cessation of life; Clinical; Clinical Research; Clinical Trials; Comprehensive Cancer Center; Connecticut; DNA Sequence Alteration; Development; Diagnosis; Disease; Drug resistance; Environment; Epidermal Growth Factor Receptor; Epigenetic Process; Frequencies; Funding; Gene Expression Alteration; Generations; Genetic; Genomics; Goals; Grant; Human; Human Cell Line; Immune; Immune response; Immunologics; Immunooncology; Immunosuppressive Agents; Immunotherapy; In Vitro; Liquid substance; Lung Adenocarcinoma; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic Neoplasm to the Central Nervous System; Metastatic malignant neoplasm to brain; Molecular; Morbidity - disease rate; Mutation; Myeloid Cells; Neoplasm Metastasis; Neuraxis; Non-Small-Cell Lung Carcinoma; Outcome; Pathology; Pathway interactions; Patients; Pharmacology; Physicians; Play; Pre-Clinical Model; Production; Proteins; Protocols documentation; Recording of previous events; Refractory Disease; Reproduction spores; Research; Research Personnel; Resistance; Resistance development; Resource Sharing; Role; Sampling; Scientist; Selection for Treatments; Solid Neoplasm; Source; Speed; Structure; T-Lymphocyte; Testing; Translating; Tyrosine Kinase Inhibitor; United States; Yale Cancer Center; anticancer research; base; bench to bedside; biomarker development; biomarker evaluation; cancer cell; cancer drug resistance; cancer therapy; career; clinical application; clinical care; clinically actionable; combat; design; effectiveness evaluation; improved; in vivo; innovation; macrophage; mortality; mouse model; mutant; next generation; novel; novel therapeutic intervention; novel therapeutics; outreach; personalized medicine; prevent; programmed cell death ligand 1; programs; prospective; resistance mechanism; sialic acid binding Ig-like lectin; targeted treatment; translational cancer research; translational research program; translational scientist; translational study; tumor; tumor microenvironment; tumor progression

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.

肺癌中的耶鲁孢子 (YSILC) 总体摘要 原发性和转移性肺癌的生物学和个性化治疗：YSILC 联合起来 跨越癌症研究不同领域的转化科学家致力于解决癌症研究的挑战 肺癌。 YSILC 的目标是通过开发新型药物来降低肺癌死亡率 基于对靶向生化和治疗的理解的疗法和治疗方法 免疫学途径涉及肺癌的进展、耐药性的获得和发展 转移 YSILC 转化研究团队将通过三个项目实现这一目标： 项目 1：测试 Siglec-15 (S15) 是 PD-L1/B7-H1 阴性患者的主要免疫抑制剂的假设 肺癌，并且阻断 S15 对一部分肺癌患者可能有效；项目2： 评估基于机制的方法来对抗 EGFR 突变肺中的酪氨酸激酶抑制剂耐药性 癌症;项目3：针对肺癌转移和中枢神经系统耐药性。那里 是三个核心（管理；生物统计学和生物信息学；以及生物样本、病理学和基因组学） 支持项目及其临床目标、机制研究和临床生物标志物评估 应用。强大的发展研究和职业提升计划（DRP、CEP） 还提出了选择具有良好成果的多样化和富有成效的项目的历史。高度 协调的 YSILC 项目、核心和计划专注于开发新型肺癌疗法， 患者样本分析、细胞分析、人类细胞系和疾病动物模型的生产 作为设计前瞻性试验的指南，将这些创新的靶向方法转化为临床治疗。 每个项目都有一项临床试验（研究者发起的或基于 NCI 的），旨在测试 新疗法的敏感性和耐药性与分子相关。预期的转化成果 该计划包括：（1）高度协调和集中地开发发现的新型免疫剂 在我们当前的 SPORE 研究期间； (2) 加深对遗传和表观遗传机制的认识 对 EGFR 疗法的耐药性以及如何应对； (3)了解大脑的机制 转移; （4）通过开发下一代肺癌扩大研究广度 研究人员并鼓励其他领域的知名研究人员进行肺癌研究 通过我们的 CEP 和 DRP 计划。