TUMOUR-HOST INTERACTIONS IN LIVER CANCER OF CHILDHOOD AND ADULTS

儿童和成人肝癌中肿瘤与宿主的相互作用

• 批准号: 10100127
• 金额: $ 148.94万
• 依托单位: NEWCASTLE UNIVERSITY
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10100127
• 关键词: TUMOUR; HOST; INTERACTIONS; LIVER; CANCER

Liver cancer is a major health problem with ~1 million cases diagnosed each year (~90,000 cases/year in Europe), and it is the 3rd cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC) in adults, and hepatoblastoma (HB) in children are considered poorly understood cancers. HCC is a difficult-to-cure cancer (curation rate ~ 30%) with poor outcome (median survival < 2 years in advanced stages), due to limited understanding of at-risk populations, resistance to therapies and lack of precision oncology. In HB, outcomes are hampered in one fourth of cases due disease progression after surgical intervention and adjuvant chemotherapy. THRIVE aims by to improve the outcome of both paediatric and adult liver cancer patients by understanding at-risk populations, tumour-host interactions, and by developing biomarkers for current therapies and novel, affordable treatments to overcome resistance. THRIVE brings together a strong, multidisciplinary team -13 partners, from 8 countries- with complementary expertise to leverage cutting-edge technologies (single-cell RNASeq, spatial transcriptomics, microbiota analysis, artificial intelligence, mouse models and patient-derived organoids) and sectors (i.e academia, SMEs, hospitals, patient associations) and 15 patient cohorts (~6,700 samples). THRIVE expects to: 1) Define molecular features of cancer predisposition and at-risk populations for development of liver cancer. 2) Develop a complete human liver cancer blueprint of tumour, immune, stromal cells and intra-tumoral microbiomes. 3) Identify AI-based and molecular markers of response to treatments. 4) Implement a preclinical drug testing platform for discovery of affordable therapies with high social impact. 5) Maximize the impact in the European society by integrating SSH disciplines, delivering accessible and re-usable data and tools to support EU initiatives such as the UNCAN.eu platform, and by influencing policymakers and health professionals. This action is part of the Cancer Mission cluster of projects on “Understanding (tumour-host interactions)".

肝癌是一个主要的健康问题，每年约有100万例确诊病例（欧洲约9万例/年），是全球癌症相关死亡的第三大原因。成人肝细胞癌（HCC）和儿童肝母细胞瘤（HB）被认为是人们知之甚少的癌症。HCC是一种难以治愈的癌症（治愈率约30%），预后差（晚期中位生存期< 2年），原因是对高危人群的了解有限，对治疗的耐药性和缺乏精确的肿瘤学。在HB中，由于手术干预和辅助化疗后疾病进展，四分之一的病例预后受到阻碍。THRIVE的目标是通过了解高危人群、肿瘤与宿主的相互作用，以及通过开发当前疗法的生物标志物和新的、负担得起的治疗方法来克服耐药性，从而改善儿科和成人肝癌患者的预后。THRIVE汇集了一个强大的多学科团队——来自8个国家的13个合作伙伴——并具有互补的专业知识，以利用尖端技术（单细胞RNASeq，空间转录组学，微生物群分析，人工智能，小鼠模型和患者来源的类器官）和部门（即学术界，中小企业，医院，患者协会）和15个患者队列（约6700个样本）。THRIVE希望：1)确定癌症易感性的分子特征和肝癌发展的高危人群。2)建立完整的人肝癌肿瘤、免疫、基质细胞和肿瘤内微生物组的蓝图。3)识别基于人工智能和分子的治疗反应标志物。4)建立临床前药物测试平台，以发现可负担且具有高社会影响的治疗方法。5)通过整合SSH学科，提供可访问和可重复使用的数据和工具，以支持UNCAN等欧盟倡议，最大限度地提高对欧洲社会的影响。欧盟平台，以及通过影响决策者和卫生专业人员。这一行动是癌症使命“理解（肿瘤-宿主相互作用）”项目集群的一部分。