Pancreatic Cancer ARTNet Center

胰腺癌 ARTNet 中心

• 批准号: 10518243
• 负责人: Pankaj Kumar Singh
• 金额: $ 128.43万
• 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/10518243
• 关键词: Advisory Committees; Biological Assay; Blood Circulation; CRISPR/Cas technology; Cancer Center; Cancer Patient; Caring; Cells; Clinic; Clinical; Clinical Trials; Collaborations; Combined Modality Therapy; Companions; Data; Development; Disease; Educational workshop; Epigenetic Process; Exposure to; Fostering; Goals; Growth; Immune; Intercellular Fluid; Investigation; Knowledge; Leadership; Libraries; Malignant neoplasm of pancreas; Mediating; Mediator of activation protein; 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; Therapeutic; Translational Research; Validation; Work; base; cancer cell; cancer therapy; cell stroma; chemotherapy; data management; 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; targeted treatment; therapy resistant; tissue resource; tool; 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.

摘要 胰腺癌患者表现出极差的预后，这至少部分是由于对 目前的标准护理化疗。虽然胰腺肿瘤对 化疗，暴露于化疗会导致获得性耐药性的发展。回应和 肿瘤细胞及其伴生物对化疗药物的耐药性受信号和代谢变化的调节 免疫和非免疫间质的变化。主要进展如下：(A)了解植物的信号反应 癌细胞和间质治疗，(B)了解代谢对信号和环境的适应 应激源，(C)开发新的治疗组合，以改善对电流的长期反应 护理标准化疗，以及(D)协调NCI领导层的研究/翻译工作，将 在靶向/预防获得性治疗耐药方面提供无与伦比的进展。Artnet中心 胰腺癌(ACPC)打算通过一个综合的研究主题来实现这些目标 肿瘤细胞获得性耐药代谢和信号介质的联合研究 胰腺癌间质重塑将导致新的有效的治疗方法以改善患者的预后。 将通过领导层、IAC、EAC、Artnet网络的合理指导来促进ACPC内的研究 和NCI计划。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变化以及肿瘤-间质代谢的串扰 胰腺导管腺癌(PDAC)获得性耐药我们假设我们独特的 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、业务设计和强有力的机构支持将推动变革性的进展 在获得的治疗耐药领域，将与Artnet的其他成员和NCI的成员保持一致 该项目的使命。对信号和代谢的机制方面提供了新的见解 机制，提出的基础研究和翻译研究将最终推动小说的发展 可以改变癌症治疗临床进程的治疗组合。这将通过以下方式实现 目的1.研究肿瘤界面获得性耐药的新机制-- 间质代谢串扰和检查临床前疗效的确定靶点，以提高治疗 对胰腺癌的反应。目标2.提供强大而创新的工具集和资源以进行调查 并验证了获得性治疗抵抗的机制。目标3.促进系统级机制 了解获得性治疗耐药机制。