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: 9338869
• 负责人: Roy S Herbst
• 金额: $ 71.51万
• 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 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338869
• 关键词: American; Animal Disease Models; Animal Model; Behavior Therapy; Biochemical; Biofeedback; Bioinformatics; Biological; Biological Assay; Biological Markers; Biology; Biometry; CBL gene; Cancer Center; Cancer Etiology; Cancer Hospital; Cancer Patient; Cell model; Cells; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Clinical Research; Clinical Trials; Collaborations; Comprehensive Cancer Center; Connecticut; DNA Sequence; Data; Development; Diagnosis; Disease; Drug resistance; Effectiveness; Environment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Evaluation; Evaluation Studies; FRAP1 gene; Foundations; Generations; Genomics; Goals; Health; Human Cell Line; Immunobiology; Immunotherapeutic agent; Investigation; Israel; Lung Adenocarcinoma; Lung nodule; Malignant Neoplasms; Malignant neoplasm of lung; Medical center; Methods; MicroRNAs; Mutation; Non-Small-Cell Lung Carcinoma; Outcome; PDCD1LG1 gene; Pathogenesis; Pathology; Pathway interactions; Patients; Physicians; Platinum; Population; Prevention strategy; Production; Prospective Studies; Recurrence; Regimen; Research; Research Personnel; Resistance; Resource Sharing; Role; Sampling; Scientist; Selection for Treatments; Seminal; Smoke; Smoking Cessation Intervention; Subgroup; Supportive care; Survival Rate; Testing; Therapeutic; Therapeutic antibodies; Tobacco; Tobacco Dependence; Toxic effect; Translating; Translational Research; Tyrosine Kinase Inhibitor; United States; Untranslated RNA; Yale Cancer Center; anticancer research; base; biomarker evaluation; cancer therapy; career; career development; clinical application; clinical care; design; efficacy testing; experience; high risk; imaging biomarker; improved; individualized prevention; innovation; miRNA expression profiling; mortality; mutant; nanoparticle; new therapeutic target; next generation; novel; novel strategies; novel therapeutic intervention; novel therapeutics; outreach; patient population; personalized approach; personalized medicine; phase 2 study; pre-clinical research; prevent; programs; prospective; research study; resistance mechanism; response; smoking cessation; targeted treatment; therapeutic target; therapy resistant; translational study; tumor; tumor progression

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.

描述（由申请人提供）：肺癌（YSILC）的耶鲁孢子结合了转化科学家，跨越了癌症研究的各个方面，以汇聚在肺癌问题上。 YSILC利用现有的耶鲁癌症中心（YCC）的优势，包括免疫生物学，microRNA研究，具有获得耐药性的抗EGFR治疗的经验以及戒烟的行为干预措施/生物学基础。 YSILC计划的目的是通过了解涉及肺癌进展的可目标生物化学和免疫学途径的新型治疗和个性化预防策略来提高肺癌患者的总体存活率，并逐渐涉及肺癌进展的习惯。 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：通过发现对抗PD-1和抗PD-1和抗B7-H1（PD-L1）疗法的反应和抗性的基础机制来开发和测试新型治疗剂；具体目标2：评估非编码microRNA作为靶向疗法的潜力；特定目标3：了解并靶向突变/抗性肺癌中的EGFR途径；特定目标4：开发和测试一种新的个性化方法获得固定消息传递的功效，以改善无症状的肺结核继续吸烟的美国人的戒烟；和特定目的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肺癌的下一代转化调查人员。提出了三个核心（行政；生物统计学和生物信息学；以及生物传染性，病理和基因组学）来支持项目及其临床目的，机械研究和对临床应用生物标志物的评估。高度协调的YSILC项目，核心和计划的重点是开发新型的肺癌疗法，分析患者样品，基于细胞的测定，人类细胞系和疾病的动物模型，作为设计前瞻性试验的指南，这些试验转化了这些创新的针对性的临床治疗方法。该计划的预期翻译结果包括：（1）新型肺癌疗法的高度协调和重点发展； （2）对PD-1/B7-H1阻断和EGFR疗法的抗药性途径的了解得以提高，包括克服/预防这些影响的前瞻性研究； （3）对患者miRNA的治疗潜力的理解； （4）在探索相关机械标记时开发有效的戒烟方法； （5）下一代研究人员的发展。