Mesothelioma, Mesothelioma; Lung, Mesotheliomas Pleural
Conditions
Keywords
pleura, mesothelioma, PPM patients, lung, Gene expression profiling, Immune microenvironment
Brief summary
Pleural and peritoneal mesotheliomas (PPM) are rare cancers mostly related to asbestos-exposure, which are characterized by a complex histopathological diagnosis and staging, few therapeutic options and a dismal prognosis. The main unmet medical need in PPM is the lack of a treatment sequence for affected patients. The advent of immune checkpoint inhibitors has changed the first line treatment of PPM, thanks to the improvement in survival achieved by the combination of ipilimumab and nivolumab that are currently approved for non-epithelioid histology in our Country. PPM is characterized by a large heterogeneity of the genomic landscape, which is mainly characterized by the loss of tumour suppressor genes and mutations in DNA repair genes and by an altered- suppressed or excluded tumor immune microenvironment (TIME). The goal of this project is to improve the immune-biological and molecular stratification of PPM subgroups that can lead to the identification of different personalized treatment approaches. PPM patients (N=220) will be retrospectively (N=150) and prospectively (N=70) recruited from the coordinator center and 6 participating Italian centers. Treatment-naïve tumor samples will be collected and analyzed by bulk gene expression and spatial whole transcriptome analysis, and by 9-color multiplex immunofluorescence. New targets or actionable pathways potentially emerging from such studies will be finally assessed and validated in patient-derived organoids/xenografts that accurately reflect PPM tumorigenesis.
Interventions
OTHERTranslation analysis
Bulk GEP analysis, Spatial whole transcriptome analysis, mIF analysis of tumors
Sponsors
Istituto Oncologico Veneto IRCCS
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with Mesothelioma of the Pleura and Peritoneum * Age greater than 18 years of age * Patients undergoing surgery will require both biopsy and surgical sampling material * Pathologist's confirmation of the presence of tumor sections in the excised specimens * Patients in follow-up from active cancer treatment for at least 6 months
Exclusion criteria
* Inadequacy of biological material for analysis under study * Patients not amenable to active oncologic treatment * Patients lost to follow-up before 6 months after the end of active oncologic treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome | Through study completion, an average of 3 years | PPM treatment-naïve tumor samples and classification in different clusters according to the differential expression of molecular and gene signatures by Gene expression profile (GEP) analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcome | Through study completion, an average of 3 years | Characterization and quantification of immune cell distribution and their spatial relationships in treatment naïve tumor samples of PPM patients will be performed by a 9-color multiplex immunofluorescence (mIF) analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Third outcome | Through study completion, an average of 3 years | In vitro and in vivo models of PPM for the investigation of activated signatures, new therapeutic targets and drug sensitivity tests. will be performed by: * development of in vitro 'organ-like' 3D structures (PDOs) derived from patient tumor tissue; * patient-derived xenograft (PDX) from PPM patients; * matched comparison of histological and molecular features of PDOs and PDXs with the original tumor tissues; * drug sensitivity/resistance tests in vitro and in vivo. |
Countries
Italy
Contacts
Primary ContactGiulia Pasello, MD
Backup ContactGian Luca De Salvo, MD
Outcome results
None listed