Selective Targeting of Pancreatic Cancer SPORE

选择性靶向胰腺癌孢子

• 批准号: 10705564
• 负责人: Jen Jen Yeh
• 金额: $ 205.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 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/10705564
• 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

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.

停止癌孢子摘要 胰腺癌仍然是一种致命的疾病，治疗选择有限。选择的选项增加了 最近5年，进行了大量的基因组分析和临床前的努力。但是，目的地进展，胰腺癌 仍然是致命疾病，五年生存率为10％，预计胰腺癌死亡 到2030年，乳房，前列腺和大肠癌的死亡都成为第二大主要原因 癌症死亡。该事件正在迅速增加，自2010年以来增长了23％，自从以来增长了57％ 2006年。与躯体的复杂相互作用的病因和近期崛起的理解仍然很差 在老龄化的情况下，遗传，基因组，表观遗传和环境因素。 与许多实体瘤不同，仅突变就不足以产生治愈性靶向疗法， 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： 低肿瘤细胞性会阻碍遗传和基因组研究，包括无法鉴定 生物标志物/亚型调整疗法 ·化学疗法和靶向治疗抗性肿瘤细胞群体 ·可能促进肿瘤和抑制肿瘤的脱糖性基质 由于抑制性髓样细胞和T效应细胞的缺乏，免疫抑制环境 ·精度肿瘤学方法仍然有限 临床试验一次仅限1-2疗法 我们组建了三个直接解决这些问题的项目；每个都有一个嵌入的早期阶段 临床试验将产生患者样本，以测试我们的孢子假设。强大的发展 根据UNC的非常成功的模型包括研究和职业增强计划 Lineberger。这些将得到一项实质性的机构承诺的支持。一个高度成就 多个研究人员的多学科团队已提出了几个机构的合作 共同包括那些做出创新和高影响力的人，交付的临床 护理并进行了临床并将其转化为胰腺癌。认识到需求 对于胰腺癌，快速转化为诊所，我们的组织采购，病理和基因组学 核心和综合定量科学核心与项目无缝地处理和分析 数据。我们的停止癌症孢子的目标是建立一个不受限制的临床试验设计范式 进行单一疗法或生物标志物。