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

描述（由申请人提供）：耶鲁肺癌 SPORE (YSILC) 联合了癌症研究各个方面的转化科学家，致力于解决肺癌问题。 YSILC 利用耶鲁大学癌症中心 (YCC) 的现有优势，包括免疫生物学、microRNA 研究、具有获得性耐药性的抗 EGFR 治疗经验，以及戒烟的行为干预/生物学基础。 YSILC 项目的目标是基于对肺癌进展和治疗耐药性获得中涉及的靶向生化和免疫途径的了解，通过开发新的治疗方法和个性化预防策略来提高肺癌患者的总体生存率。 YSILC 转化研究团队将通过五个具体目标来实现这一目标： 具体目标 1：通过发现抗 PD-1 和抗 B7-H1 (PD-L1) 疗法的反应和耐药机制来开发和测试新疗法；具体目标 2：评估非编码 microRNA 作为靶向治疗的潜力；具体目标3：了解并靶向突变/耐药肺癌中的EGFR通路；具体目标 4：开发并测试一种新的个性化方法的有效性，以获取框架消息传递，以改善患有无症状肺结节但继续吸烟的美国人的戒烟情况；具体目标 5：通过发展研究计划和职业发展计划，开发新的研究方向并培养下一代肺癌转化研究人员。提出三个核心（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）来支持这些项目及其临床目标、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、核心和计划专注于开发新型肺癌疗法，以患者样本分析、细胞分析、人类细胞系和疾病动物模型的生产为指导，设计前瞻性试验，将这些创新的靶向方法转化为临床疗法。该项目的预期转化成果包括：（1）高度协调、重点突出的新型肺癌疗法的开发； (2) 更好地了解 PD-1/B7-H1 阻断和 EGFR 疗法的耐药途径，包括克服/预防这些影响的前瞻性研究； (3) 了解 miRNA 对患者的治疗潜力； (4) 开发有效的戒烟方法，同时探索相关的机制标志； (5) 下一代研究者的发展。

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.