Selective Targeting of Pancreatic Cancer SPORE

抗癌孢子提取液 胰腺癌仍然是一种致命的疾病，治疗选择有限。在过去的几年中，选择增加了 过去5年，通过大量的基因组分析和临床前的努力。然而，尽管取得了进展，胰腺癌 仍然是一种致命的疾病，五年存活率为10%，预计死于胰腺癌 到2030年超过乳腺癌、前列腺癌和结直肠癌的死亡人数，成为全球第二大癌症死因 癌症死亡。发病率正在迅速上升，自2010年以来增长了23%，自2010年以来增长了57% 2006年。最近上升的病因和原因仍然不太清楚，因为体细胞 人口老龄化背景下的遗传、基因组、表观遗传和环境因素。 与许多实体肿瘤不同，单靠突变还不足以产生根治性的靶向治疗， 临床有用的生物标志物或共识亚型。仍然存在的挑战包括： ·肿瘤细胞密度低阻碍了遗传和基因组研究，包括无法识别 用于量身定制治疗的生物标记物/亚型 ·耐化疗和靶向治疗的肿瘤细胞群 ·促结缔组织间质，可能同时促进肿瘤和抑制治疗 ·由于髓系细胞抑制和T效应细胞稀少而造成的免疫抑制环境 ·精确的肿瘤学方法仍然有限 ·临床试验一次仅限于1-2种疗法 我们已经组织了三个直接解决这些问题的项目；每个项目都有一个嵌入的早期阶段 临床试验将产生患者样本，用来检验我们的孢子假说。稳健发展 根据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。这些措施将得到大量机构承诺的支持。一个非常有成就的人 多学科的调查团队与几个机构的合作已经带来 这些人加在一起，包括那些做出了创新性和重大影响的贡献、提供临床 护理并进行与胰腺癌密切相关的临床和翻译研究。认识到需要 对于胰腺癌的快速转化到临床，我们的组织采购，病理学和基因组学 核心和综合量化科学核心与项目无缝协作以进行处理和分析 数据。我们阻止癌症孢子的目标是建立一种不受限制的临床试验设计的新范式 单一疗法或生物标记物。

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.