Colorectal Cancer, Ovarian Cancer, Secondary Peritoneal Cancers
Conditions
Keywords
peritoneal carcinomatosis, tumor heterogeneity, epigenetic landscape
Brief summary
How epigenetic deregulation affects gene expression patterns in subclones of the same tumor is poorly known. Peritoneal Carcinomatosis (PC) is a condition in which multiple metastases of the same abdominal tumor develop in the peritoneal cavity and intra-peritoneal organs, thus defining different ecosystems of the same cancer. PITCHER addresses the variations in epigenetically regulated gene expression between different subclones of PC in relation with cell mechanoresponses, providing insights on how cancer epigenetic landscapes evolve under environmental pressures and on strategies used by cancer cells to adapt to the transition from one ecosystem to the other. PITCHER is a network of 10 teams from Lyon, Grenoble and Marseille, based on data and specimen collection of patients who have undergone a surgery for a peritoneal carcinomatosis of ovarian or colorectal origin. PC lesions and eventually matched specimens of primary tumors will be collected in the same patients at the time of the surgery or eventually retrieved from already existing samples. Epigenetic landscapes will be analyzed by a bioinformatics pipeline combining exome sequencing, transcriptome and methylome to identify epigenetic hotspots, and their variations across lesions will be evaluated. These analyses will be realized in fresh (when available) or pre-existing samples. When possible, organoid cultures and animal models will be derived from multicellular structures in peritoneal fluids and membrane, cytoskeletal and nucleoskeletal mechanoresponses will be characterized using Atomic Force Microscopy. The role of tumor axonogenesis, a process of neo-formation of axon fibers in tumors, will be addressed. Experimental studies of cell responses to therapy will be performed to derive mathematical predictive models. All components will be integrated in a systems biology map of PC.
Interventions
OTHERconstruction of a database of genetic and epigenetic data on peritoneal carcinomatosis of colorectal or ovarian origin.
Construction of a core database of genetic and epigenetic markers, in order to identify predictive biomarkers and potentially actionable targets for controlling the spread of peritoneal carcinomatosis.
Sponsors
Hospices Civils de Lyon
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who accept to participate to the study * Men / women aged over 18 years * Patients with cancer management and care for peritoneal carcinomatosis of digestive or ovarian origin * Patients had histologic/radiologic confirmation of peritoneal disease * Serology negative HIV, HEPATITIS
Exclusion criteria
• none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| genetic and epigenetic data available for 20 multiplets biospecimens (peritoneal carcinomatosis + healthy tissue + primary tumor + tissue from other tumor metastasis - when applicable and available- ) | end of the inclusion period (September 2022) | The main endpoint is to implement a specific tissue collection of appropriate quality, assembling multiplets of biospecimens from the same patient, in order to construct a core database for research on mechanisms, biomarkers and actionable therapeutic targets in PC. This database will include molecular analysis by next-generation sequencing of whole-exome genetic, transcriptomic and epigenetic patterns of primary, peritoneal and metastatic lesions. Omics data are compiled using a data model also including anonymized information on histopathology and clinical history of treatments (when applicable) |
Countries
France
Contacts
Primary ContactOlivier GLEHEN, MD
Backup ContactSara CALATTINI, CRA
Outcome results
None listed