TUMOUR-HOST INTERACTIONS IN LIVER CANCER OF CHILDHOOD AND ADULTS

肝癌是一个主要的健康问题，每年约有100万例确诊病例(欧洲约为9万例/年)，是全球与癌症相关的死亡的第三大原因。成人肝细胞癌(HCC)和儿童肝母细胞瘤(HB)被认为是知之甚少的癌症。肝癌是一种难以治愈的癌症(治愈率~30%)，由于对高危人群的了解有限，对治疗的抵抗力和缺乏精确的肿瘤学，结果很差(中位生存期和晚期患者2年)。在乙肝患者中，四分之一的病例在手术干预和辅助化疗后，由于疾病进展而影响预后。Thrive的目标是通过了解高危人群、肿瘤与宿主的相互作用，以及为目前的治疗方法和新的、负担得起的治疗方法开发生物标记物来克服耐药性，改善儿童和成人肝癌患者的预后。Thrive汇集了一支强大的多学科团队--来自8个国家的13个合作伙伴--具有互补的专业知识，以利用尖端技术(单细胞RNA序列、空间转录学、微生物区系分析、人工智能、老鼠模型和患者衍生的有机物)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6,700个样本)。Thrive希望：1)确定癌症易感性和肝癌高危人群的分子特征。2)制定完整的人类肝癌的肿瘤、免疫、基质细胞和瘤内微生物的蓝图。3)确定基于人工智能和分子标记的处理反应标记。4)实施临床前药物检测平台，发现社会影响大、负担得起的治疗方法。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，以支持诸如UNCAN.eu平台等欧盟倡议，并通过影响政策制定者和卫生专业人员，最大限度地提高对欧洲社会的影响。这项行动是癌症使命“了解(肿瘤-宿主相互作用)”项目集群的一部分。

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)".