Selective Targeting of Pancreatic Cancer SPORE

选择性靶向胰腺癌孢子

基本信息

批准号：
10845917
负责人：
Jen Jen Yeh
金额：
$ 8.4万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-16 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10845917
关键词：
Address Advocate Area Biological Markers Cancer Etiology Cellularity Cessation of life Clinic Clinical Research Clinical Trials Clinical Trials Design Collaborations Colorectal Cancer Complex Consensus Consent Data Dedications Desmoplastic Development Diagnosis Disease Environment Environmental Risk Factor Epigenetic Process Etiology Frequencies Gene Mutation Generations Genetic Genomics Goals Immunosuppression Incidence Industry Institution International KRAS2 gene Lead Malignant Neoplasms Malignant neoplasm of pancreas Malignant neoplasm of prostate Modeling Mutation Myeloid-derived suppressor cells Names Neoadjuvant Therapy Pancreatic Ductal Adenocarcinoma Pathology Patients Pilot Projects Population Prevalence Process Research Research Personnel Sampling Science Solid Neoplasm Survival Rate T cell therapy T-Lymphocyte Testing Therapeutic Time Tissue Procurements Tissues Translational Research Translations Tumor Promotion Work aging population biomarker identification career chemotherapy chimeric antigen receptor T cells clinical biomarkers clinical care combinatorial design early phase clinical trial effector T cell individualized medicine innovation malignant breast neoplasm multidisciplinary neoplastic cell next generation novel novel therapeutics oncology trial pancreatic cancer patients pre-clinical precision oncology programs recruit research and development targeted treatment therapy resistant translational goal translational scientist translational therapeutics tumor tumor microenvironment tumor-immune system interactions

项目摘要

SToP CANCER SPORE ABSTRACT Pancreatic cancer remains a lethal disease with limited therapeutic options. Options have increased over the last 5 years, with large genomic analyses and preclinical efforts. However, despite advances, pancreatic cancer remains a lethal disease with a five-year survival rate of 10%, and deaths from pancreatic cancer are expected to surpass deaths from breast, prostate and colorectal cancer by 2030, to become the second leading cause of cancer deaths. The incidence is rapidly increasing, with, a 23% increase since 2010 and 57% increase since 2006. The etiology and reason for the recent rise remain poorly understood with a complex interplay of somatic genetic, genomic, epigenetic and environmental factors in the context of an aging population. Unlike many solid tumors, mutations alone have not been sufficient to yield curative targeted therapies, clinically useful biomarkers or consensus subtypes. Challenges that remain include: · Low tumor cellularity hampers both genetic and genomic studies, including the inability to identify biomarkers/subtypes to tailor therapies · Chemotherapy and targeted therapy resistant tumor cell populations · Desmoplastic stroma that may be both tumor promoting and therapy inhibiting · Immunosuppressive environment due to suppressive myeloid cells and a paucity of T effector cells · Precision oncology approaches are still limited · Clinical trials are limited to only 1-2 therapies at a time We have assembled three projects that directly address these issues; each has an embedded early phase clinical trial that will yield patient samples with which to test our SPORE’s hypotheses. Robust Development Research and Career Enhancement Programs are included based on the highly successful models at UNC Lineberger. These will be backed by a substantial institutional commitment. A highly accomplished multidisciplinary team of investigators with collaborations across several institutions have been brought together that includes those who have made innovative and high impact contributions, delivered clinical care and performed clinical and translational research germane to pancreatic cancer. Recognizing the need for pancreatic cancer rapid translation to the clinic, our Tissue Procurement, Pathology, and Genomics Core and Integrative Quantitative Sciences Core work seamlessly with the projects to process and analyze data. Our SToP Cancer SPORE goal is to establish a new paradigm for clinical trial design that is not limited to a single therapy or biomarker.

阻止癌症孢子摘要胰腺癌仍然是一种致命的疾病，治疗选择有限。然而，尽管取得了进展，但胰腺癌在过去 5 年中进行了大量的基因组分析和临床前研究。仍然是一种致命疾病，五年生存率为 10%，预计胰腺癌会导致死亡到 2030 年，癌症死亡人数将超过乳腺癌、前列腺癌和结直肠癌，成为导致癌症死亡的第二大原因癌症死亡人数正在迅速增加，自 2010 年以来增加了 23%，自 2010 年以来增加了 57%。 2006. 由于躯体细胞之间复杂的相互作用，最近发病率上升的病因和原因仍然知之甚少。人口老龄化背景下的遗传、基因组、表观遗传和环境因素。与许多实体瘤不同，仅突变不足以产生有效的靶向治疗，临床上有用的生物标志物或共识亚型仍然存在的挑战包括： · 低肿瘤细胞构成阻碍了遗传和基因组研究，包括无法识别生物标志物/亚型来定制治疗方法 · 化疗和靶向治疗耐药的肿瘤细胞群 · 促纤维增生基质可能既促进肿瘤又抑制治疗 · 由于抑制性骨髓细胞和效应 T 细胞的缺乏而导致的免疫抑制环境 · 精准肿瘤学方法仍然有限 · 临床试验一次仅限于 1-2 种疗法我们组建了三个直接解决这些问题的项目；每个项目都有一个嵌入式的早期阶段；临床试验将产生患者样本来测试我们的 SPORE 的稳健发展假设。基于北卡罗来纳大学非常成功的模式，包括研究和职业提升计划莱恩伯格：这些将得到大量机构承诺的支持。跨多个机构合作的多学科研究团队已经成立包括那些做出了创新和高影响力贡献的人一起，提供了临床认识到这种需要，并进行了与胰腺癌密切相关的临床和转化研究。为了将胰腺癌快速转化为临床，我们的组织采购、病理学和基因组学核心和综合定量科学核心与项目无缝协作以进行处理和分析我们的 STOP Cancer SPORE 目标是建立不受限制的临床试验设计新范例。单一疗法或生物标志物。