Pancreatic Cancer ARTNet Center

胰腺癌 ARTNet 中心

• 批准号: 10707504
• 负责人: Pankaj Kumar Singh
• 金额: $ 126.6万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707504
• 关键词: Advisory Committees; Biological Assay; CRISPR screen; Cancer Center; Cancer Patient; Caring; Cells; Circulation; Clinic; Clinical; Clinical Trials; Collaborations; Combined Modality Therapy; Companions; Data; Data Coordinating Center; Dedications; Development; Disease; Educational workshop; Epigenetic Process; Exposure to; Fostering; Goals; Growth; Immune; Institution; Intercellular Fluid; Investigation; Knowledge acquisition; Leadership; Libraries; Malignant neoplasm of pancreas; Mediating; Mediator; Metabolic; Methods; Mission; Modification; National Cancer Institute; Outcome; Paclitaxel; Pancreatic Ductal Adenocarcinoma; Patients; Primary Neoplasm; Prognosis; Proteins; Recording of previous events; Research; Resistance; Resource Sharing; Resources; Role; Sampling; Science; Scientist; Signal Transduction; Site; Stromal Cells; Stromal Neoplasm; System; Technology; Therapeutic; Translations; Validation; Work; cancer cell; cancer therapy; chemotherapy; design; effective therapy; environmental stressor; exosome; improved; innovation; insight; lectures; lipidomics; meetings; member; metabolic phenotype; metabolomics; neoplastic cell; novel; novel therapeutics; pancreatic cancer patients; pancreatic neoplasm; patient prognosis; preclinical efficacy; prevent; programs; resistance mechanism; response; single-cell RNA sequencing; skills; sound; stable isotope; standard of care; survival outcome; symposium; synergism; targeted treatment; therapy resistant; tissue resource; tool; translational potential; translational study; treatment response; tumor metabolism; web site

Abstract Pancreatic cancer patients show an extremely poor prognosis, which is at least in part due to poor response to the current standard-of-care chemotherapies. While pancreatic tumors present an inadequate response to chemotherapy, exposure to chemotherapy leads to development of acquired resistance. The response and resistance to chemotherapies are modulated by signaling and metabolic alterations in tumor cells and companion changes in the immune and non-immune stroma. Major advances in (a) understanding signaling responses of cancer cells and stroma to therapy, (b) understanding metabolic adaptations to signaling and environmental stressors, (c) development of novel therapeutic combinations to improve long-term response to current standards-of-care chemotherapies, and (d) coordinating research/translation efforts by NCI leadership, will provide unparalleled advances in targeting/preventing acquired therapy resistance. The ARTNet Center for Pancreatic Cancer (ACPC) intends to achieve these objectives through an integrated research theme that combined investigations into the metabolic and signaling mediators of acquired resistance in tumor cells and stromal remodeling in pancreatic cancer will lead to novel effective therapies to improve the patient prognosis. Research within ACPC will be fostered through sound guidance from leadership, IAC, EAC, ARTNet network and NCI program. The overall goal of the Center is to study innovative hypothesis-driven mechanisms of metabolic and signaling alterations in tumor cells and tumor-stromal metabolic crosstalk that contribute to acquired therapy resistance in pancreatic ductal adenocarcinoma (PDAC). We hypothesize that our unique leadership team, outstanding expertise of project and core leaders, singular set of technological capabilities and resources, operational design, and strong institutional support of the ACPC will drive transformative advances in the acquired therapy resistance field that will be in alignment with the other ARTNet members and NCI’s mission for the program. Providing novel insights into the mechanistic aspects of the signaling and metabolic mechanisms, the proposed basic and translational studies will ultimately drive the development of novel therapeutic combinations that can change the clinical course of cancer therapy. This will be achieved through the following Specific Aims: Aim 1. Investigate novel mechanisms of acquired resistance at the interface of tumor- stromal metabolic cross talk and examine the preclinical efficacy of identified targets to improve the therapeutic response against pancreatic cancer. Aim 2. Provide robust and innovative toolsets and resources to investigate and validated mechanisms of acquired therapy resistance. Aim 3. Facilitate a systems-level mechanistic understanding of acquired therapy resistance mechanisms.

抽象的 胰腺癌患者的预后极差，这至少部分是由于对胰腺癌的反应不佳 而目前的标准护理化疗对胰腺肿瘤的反应不足。 化疗，接触化疗会导致获得性耐药的发生。 对化疗的耐药性是通过肿瘤细胞和同伴中的信号传导和代谢改变来调节的 免疫和非免疫基质的变化在（a）理解信号反应方面取得了重大进展。 癌细胞和基质对治疗的影响，(b) 了解代谢对信号传导和环境的适应 压力源，(c) 开发新的治疗组合以改善对当前压力源的长期反应 护理标准化疗，以及 (d) NCI 领导层协调研究/翻译工作，将 在靶向/预防获得性治疗耐药方面提供了无与伦比的进步。 胰腺癌 (ACPC) 打算通过一个综合研究主题来实现这些目标： 对肿瘤细胞获得性耐药的代谢和信号传导介质的综合研究 胰腺癌的基质重塑将带来新的有效疗法，以改善患者的预后。 ACPC 内的研究将通过领导层、IAC、EAC、ARTNet 网络的良好指导来促进 该中心的总体目标是研究创新的假设驱动机制。 肿瘤细胞的代谢和信号传导改变以及肿瘤间质代谢串扰有助于 胰腺导管腺癌（PDAC）的获得性治疗耐药。 领导团队、项目和核心领导者的杰出专业知识、独特的技术能力和 ACPC 的资源、运作设计和强有力的机构支持将推动变革性进展 在获得性治疗耐药领域，这将与其他 ARTNet 成员和 NCI 保持一致 该计划的使命是提供对信号传导和代谢机制方面的新颖见解。 机制，所提出的基础和转化研究将最终推动新颖的发展 可以改变癌症治疗临床过程的治疗组合将通过以下方式实现。 具体目标如下： 目标 1. 研究肿瘤-肿瘤细胞界面获得性耐药的新机制 基质代谢串扰并检查已确定靶点的临床前疗效，以改善治疗 目标 2. 提供强大且创新的工具集和资源来进行研究。 目标 3. 促进系统级机制。 了解获得性治疗耐药机制。