Work package 1: Patient Recruitment and Harmonized Latin American–European GBC Biorepository
WP 1 includes the recruitment and interview of patients, the collection, processing and storage of biospecimens, and the retrieval of clinical information. The recruitment of patients is harmonized across all recruitment sites.
Task 1.1: Patient recruitment and interview, biospecimen collection, processing and storage, and retrieval of clinical information
Task 1.2: Recruitment harmonization across all recruitment sites
Work Package 2: Metabolic Dysfunction and Gender-Specific Factors in GBC Development
WP 2 assesses the interactive roles of diet and lifestyle patterns, their metabolic consequences, and the risk of GBC development by comparing epidemiologic data, metabolites and markers of gut barrier function and permeability, together with genetic information from diverse populations
Task 2.1: Generation of targeted and untargeted wide-spectrum metabolomics and gut barrier function marker data
Task 2.2: Assessing the association between GBC risk and dietary, lifestyle, metabolomics and gut barrier function
Task 2.3: Validation of metabolites and markers of gut barrier function as GBC biomarkers
Work Package 3: Novel Biomarkers for GBC Risk Prediction and Early Detection
WP 3 aims at the identification of epi/genetic biomarkers for gallbladder cancer risk prediction and early detection. The most promising biomarkers will be characterized on the molecular and cellular level.
Task 3.1: Identification and validation of novel GBC biomarkers for GBC risk prediction and early detection
Task 3.2: Functional characterization of identified and validated biomarkers for GBC risk and early diagnosis
Work Package 4: Novel opportunities for tertiary GBC prevention using targeted therapies
WP 4 aims to identify mutations in gallbladder cancer that are actionable for currently available targeted therapies, mutations in ARID1A and other tumour suppressor genes that might point to a synthetic lethal effect.
Task 4.1: Targeted sequencing to identify potentially actionable mutations in GBC
Task 4.2: Evaluation of the synthetic lethal effect of ARID1A in GBC cell lines
Work Package 5: IT Platform and Biostatistics
WP 5 implements an IT Platform for the collection of study data, which will then be analyzed using sophisticated statistical techniques including Mendelian randomization for the identification of causal mechanisms in gallbladder cancer development
Task 5.1: Development and utilization of an European–Latin American GBC IT Platform
Task 5.2: Statistical analysis and biostatistics consulting for members of the European–Latin American Consortium towards Eradication of Preventable GBC
Task 5.3: Use of Mendelian randomization to examine the causal mechanisms involved in GBC development
Work Package 6: Research Training
WP 6 provides excellent opportunities to the next generation of Latin American researchers to acquire interdisciplinary background expertise in GBC while at the same time specializing in statistical genetics and precision medicine.
Task 6.1: Recruitment of six selected PhD students
Task 6.2: Supervision of PhD students during a training-through-research rotation programme
Task 6.3: Advanced courses on interdisciplinary topics for researchers to qualify the next generation of Latin American PhD students in precision medicine for GBC
Work Package 7: Project Management
WP 7 ensures that the activity and overall goals of the establishment and exploitation of the EULAT Eradicate GBC consortium will be achieved within the time and budget foreseen
Task 7.1: Establish and operate a project governing body
Task 7.2: Administrative, contractual and financial management of the project
Task 7.3: Internal communication
Task 7.4: Establish and operate an External Advisory Board
Work Package 8: Ethics requirements
This work package sets out the 'ethics requirements' that the project complies with.