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

描述（由申请人提供）：耶鲁大学肺癌研究项目（YSILC）将癌症研究各个方面的转化科学家聚集在一起，共同研究肺癌问题。YSILC利用耶鲁癌症中心（YCC）现有的优势，包括免疫生物学、microRNA研究、获得性耐药的抗egfr治疗经验，以及戒烟的行为干预/生物学基础。YSILC项目的目标是通过开发新的治疗方法和个性化的预防策略来提高肺癌患者的总体生存率，这些策略基于对肺癌进展和获得治疗耐药的可靶向生化和免疫途径的理解。YSILC转化研究团队将通过五个特定目标来实现这一目标：特定目标1：通过发现抗pd -1和抗b7 - H1 （PD-L1）治疗的反应和耐药机制，开发和测试新的治疗方法；特异性目标2：评估非编码microrna作为靶向治疗的潜力；特异性目标3：了解和靶向突变/耐药肺癌中的EGFR通路；具体目标4：开发和测试一种新的个性化方法的有效性，以获得框架信息，以改善美国无症状肺结节患者继续吸烟的戒烟效果；具体目标5：通过发展研究项目和职业发展项目，开发新的研究方向，培养下一代肺癌转化研究者。三个核心（行政管理、生物统计学和生物信息学、生物标本、病理学和基因组学）被提议来支持项目及其临床目标、机制研究和临床应用生物标志物的评估。高度协调的YSILC项目、核心和项目专注于开发新型肺癌治疗方法，通过对患者样本的分析、基于细胞的分析、人类细胞系的生产和疾病的动物模型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方法。该项目的预期转化成果包括：(1)高度协调和集中的新型肺癌疗法的开发；(2)进一步了解PD-1/B7-H1阻断和EGFR治疗的耐药途径，包括克服/预防这些影响的前瞻性研究；(3)了解mirna在患者中的治疗潜力；(4)开发有效的戒烟方法，同时探索相关的机制标记；(5)下一代研究者的培养。

DESCRIPTION (provided by applicant): The Yale SPORE in Lung Cancer (YSILC) coalesces translational scientists spanning all aspects of cancer research to converge on the lung cancer problem. The YSILC leverages existing Yale Cancer Center (YCC) strengths including immunobiology, microRNA research, experience with anti-EGFR treatments with acquired resistance, and the behavioral interventions/biological underpinnings of smoking cessation. The goal of the YSILC program is to improve the overall survival rate of lung cancer patients by developing novel therapeutics and personalized prevention strategies based on an understanding of the targetable biochemical and immunological pathways involved in the progression of lung cancer and the acquisition of resistance to therapy. The YSILC translational research team will accomplish this objective through five specific aims: Specific Aim 1: Develop and test novel therapeutics by discovering the mechanisms underlying the response and resistance to anti-PD-1 and anti-B7- H1 (PD-L1) therapies; Specific Aim 2: Evaluate the potential of non-coding microRNAs as targeted therapies; Specific Aim 3: Understand and target the EGFR pathway in mutant/resistant lung cancer; Specific Aim 4: To develop and test the efficacy of a new personalized approach to gain-framed messaging to improve smoking cessation in Americans with asymptomatic lung nodules who continue to smoke; and Specific Aim 5: To develop new research directions and nurture the next generation of translational investigators in lung cancer through a Developmental Research Program and a Career Development Program. Three cores (Administrative; Biostatistics and Bioinformatics; and Biospecimen, Pathology, and Genomics) are proposed to support the projects and their clinical aims, mechanistic studies, and evaluation of biomarkers for clinical application. 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. The expected translational outcomes of the program include: (1) A highly coordinated and focused development of novel lung cancer therapies; (2) an improved understanding of resistance pathways to PD-1/B7-H1 blockade and EGFR therapies, including prospective studies to overcome/prevent these effects; (3) an understanding of the therapeutic potential of miRNAs in patients; (4) development of effective smoking cessation methods while exploring correlative mechanistic markers; and (5) the development of the next generation of investigators.