Title: Pseudomyxoma peritonei: building a European multicentric cohort to accelerate new therapeutic perspectives - Studentship
Funder: Cancer Research UK

Abstract: Pseudomyxoma peritonei (PMP) is a rare condition of mainly appendiceal origin characterized by peritoneal dissemination of mucinous tumor and, if untreated, is ultimately fatal. PMP represents a perfect paradigm of peritoneal-based malignancy amenable to intensive locoregional treatment. In fact, dramatic survival improvements have been associated with complete cytoreductive surgery and hypertermic intraperitoneal chemotherapy (CRS-HIPEC). The most common histological variants of PMP according to PSOGI classification are Low- grade Peritoneal Mucinous Carcinomatosis and high-grade Peritoneal Mucinous Carcinomatosis. This histological classification is the current most important prognostic factor. However prognosis is still unpredictable and 20-40% of low-grade disease succumb to rapidly progressive recurrent disease. Conversely, a small but significant proportion of high grade disease experiences favorable course despite the worst histology. Furthermore, the use of adjuvant systemic anticancer treatment is not standardized and PMP biology is still largely unknown. The goals of the present project are: - build a multicentric cohort of PMPs through a web-platform for collection of genomic/trascriptomic and clinical data as well as for creating a repository of tissue specimens and 3D-derived cultures; - generate global DNA/RNA-seq data from 200 retrospective cases available among the centres. Similar profiles will be obtained from 150 cases/year for 5 years from all the centres involved. - develop 3D-cellular models of PMP. Benefiting from previous experience on 3D models (organoids) and cancer stem cells of colorectal carcinomatosis we will develop similar ones that will serve to better understand PMP biology; - establish common network interlinked bio-bank for tissue specimens, blood and 3D models in each centre; - validate the prognostic value of a new transcriptional signature and of a new composite prognostic score based on gene expression profiling and PMP stromal and cellularity features that we have successfully tested in a small retrospective series. These signatures will discriminate between high and low-risk disease and, in spite of pathological features, predict with high sensitivity patient’s prognosis. - validate “druggable targets”, and to test new drugs or drug combinations. Specifically, we will assess the suitability of a preclinical platform, in which PMP organoids are subject to drug screening for selecting therapeutic candidates. - 3D models will also allow to validate potential new therapeutic targets emerging from molecular characterization of PMP by using genetic and advanced pharmacological approaches. The project will generate whole NGS-analyses on 850 PMPs, as well as a considerable number of 3D models, sharable among the partners and open to external groups.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS