Tumor-host interactions in liver cancerof childhood and adults
THRIVE is an EU-founded initiative that brings together a strong and multidisciplinary team with 13 partners, from 8 countries, with complementary expertise in liver cancer research and in the use of cutting-edge technologies
Our main focus is to enhance the outcome of paediatric and adult liver cancer patients by:
Advancing the
UNDERSTANDING
of the disease
Identifying
BIOMARKERS
for current therapies
Developing
NOVEL TREATMENTS
to overcome resistance
Why are we studying liver cancer?
1milion
new cases per year worldwide
3rd
leading cause of cancer-related mortality
87.000
Europeans diagnosed in 2020
78.000
Europeans died from liver cancer in 2020
Understanding Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults, accounting for around 90% of cases. Hepatocellular carcinoma is a difficult-to-cure cancer, with a low curation rate and with poor outcome.
About the half of all hepatocellular carcinoma patients will be treated with systemic therapies, either because they are diagnosed at advanced stages of the disease or because they progress after surgical or loco-regional therapies.
Currently, immune-based therapies stand as the standard treatment for patients with hepatocellular carcinoma at advanced stages. Despite the demonstrated improved of patient outcomes following immune therapies, a high percentage of cases do not respond to the treatment.
Key challenges in hepatocellular carcinoma research today include:
- A better understanding of the factors associated with risk of developing hepatocellular carcinoma, particularly in patients with metabolic-associated fatty liver disease (MAFLD),
- Identifying why current treatments may not always be effective,
- Developing tools that can predict how hepatocellular carcinoma patients will respond to treatment.
Addressing Liver Cancer in Children
In children, hepatoblastoma (HB) is the predominant form of liver cancer, occurring at a rate of around 2 cases per million children annually.
The standard treatment for children with hepatoblastoma involves surgical intervention followed by chemotherapy. While the majority of patients respond positively to this treatment, half of them may experience severe long-term side effects. In addition, this regimen does not achieve cure in about 30% of cases.
All this underscores the need for the identification of predictors or response to treatment, as well as novel treatments in the field of hepatoblastoma.
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Project Aims
The overall aim of the THRIVE project is to improve the outcome of both paediatric and adult liver cancer patients by understanding at-risk populations, tumour-host molecular interactions, developing biomarkers for current therapies and identify novel and affordable and societally-accepted treatments to overcome resistance.
Furthermore, we also aim to enhance the societal impact of our research, to promote FAIRness and Open Science, and to make health policy makers as well as healthcare professionals aware of the THRIVE results.
These THRIVE objectives will be tackled by the following specific aims:
Aim #1
To understand the causative processes and key determinants of liver cancer development
Aim #2
To decipher the molecular and cellular tumour–host interactions by:
- understanding the immune and stroma cell population interactions.
- exploring the intra-tumoral microbiome component
Aim #3
To develop reliable tools predicting response to immune therapies by:
- developing molecular biomarkers
- generating an AI-tool for guidance in decision making
Aim #4
To propose innovative, socially acceptable, and affordable new treatment
Aim #5
To integrate our discoveries with other EU resources and initiatives.
Aim #6
To impact health policy makers and healthcare professionals.
Work Packages
THRIVE is organised in 11 complementary and inter-related Work Packages (WP)
WP2Determinants of liver cancer
It will address an unresolved question in the field, defining key determinants of a) liver cancer development in specific cohorts of patients with metabolic-associated fatty liver disease (MAFLD), which is the leading cause of liver cancer in adults; and b) progression of hepatoblastoma, the primary form of liver cancer in children.
WP3Molecular tumour-host interactions
It will use cutting-edge molecular technologies, such as single-cell sequencing and spatial transcriptomics, to provide insights regarding tumour-host interactions in liver cancer
WP4Intratumoral microbiome
In WP4, we will dissect liver tumours from a completely unique angle, namely exploring the role of the intratumoral microbiome and its implication in tumour-host interactions.
WP5Biomarkers of response to treatment
It will be devoted at identifying biomarkers of response/resistance to immune-based therapies in hepatocellular carcinoma, and of resistance to chemotherapy in paediatric hepatoblastoma patients, considering molecular, immune and microbiome factors.
WP6Artificial-intelligence-based biomarkers of response to treatment
We will specifically develop artificial-intelligence-based tools using high-resolution histological images to further explore prediction of response in hepatocellular carcinoma and hepatoblastoma
WP7New therapies
Knowledge derived from WP2 to WP6 will fuel WP7, devoted to identifying novel therapeutic strategies aimed at overcoming resistance to the current standard-of-care therapies in childhood and adult liver cancer patients
WP8Data integration to UNCAN.eu
The UNCAN.eu initiative aims to achieve the next breakthrough needed to advance the understanding of cancer mechanisms in order to improve cancer prevention, early diagnosis and treatment, providing a basis for saving millions of European citizens’ lives
WP9Project management and coordination
It will be dedicated to the THRIVE project management and coordination
WP10Communication, dissemination and exploitation
It will deal with communication & dissemination of all THRIVE information generated, exploitation and interaction with EU funded activities.
WP11Promoting social impact
It will ensure the social impact and viability of THRIVE beyond the grant period; and promote networking, exchange of knowledge, establishment of best practices and interaction with patients and policymakers.
WP1Tissue and Data Management
It is a transversal work package and will focus on Tissues and Data Management and it is closely connected to WP2, WP3 and WP4 which will be developed in parallel
WP2Determinants of liver cancer
It will address an unresolved question in the field, defining key determinants of a) liver cancer development in specific cohorts of patients with metabolic-associated fatty liver disease (MAFLD), which is the leading cause of liver cancer in adults; and b) progression of hepatoblastoma, the primary form of liver cancer in children.
WP3Molecular tumour-host interactions
It will use cutting-edge molecular technologies, such as single-cell sequencing and spatial transcriptomics, to provide insights regarding tumour-host interactions in liver cancer
WP4Intratumoral microbiome
In WP4, we will dissect liver tumours from a completely unique angle, namely exploring the role of the intratumoral microbiome and its implication in tumour-host interactions.
WP5Biomarkers of response to treatment
It will be devoted at identifying biomarkers of response/resistance to immune-based therapies in hepatocellular carcinoma, and of resistance to chemotherapy in paediatric hepatoblastoma patients, considering molecular, immune and microbiome factors.
WP6Artificial-intelligence-based biomarkers of response to treatment
We will specifically develop artificial-intelligence-based tools using high-resolution histological images to further explore prediction of response in hepatocellular carcinoma and hepatoblastoma
WP7New therapies
Knowledge derived from WP2 to WP6 will fuel WP7, devoted to identifying novel therapeutic strategies aimed at overcoming resistance to the current standard-of-care therapies in childhood and adult liver cancer patients
WP8Data integration to UNCAN.eu
The UNCAN.eu initiative aims to achieve the next breakthrough needed to advance the understanding of cancer mechanisms in order to improve cancer prevention, early diagnosis and treatment, providing a basis for saving millions of European citizens’ lives
WP9Project management and coordination
It will be dedicated to the THRIVE project management and coordination
WP10Communication, dissemination and exploitation
It will deal with communication & dissemination of all THRIVE information generated, exploitation and interaction with EU funded activities.
WP11Promoting social impact
It will ensure the social impact and viability of THRIVE beyond the grant period; and promote networking, exchange of knowledge, establishment of best practices and interaction with patients and policymakers.
Expected outputs
Tumour microenvironment and microbiome characterization in HCC and HB
AI pipeline and biomarkers to define at risk populations for liver cancer development and for treatment response prediction.
Novel, socially accepted and affordable treatments to revert ICI resistance in HCC and chemoresistance in HB.
Evidence-based recommendations for policy makers and health professionals.
Partners
