Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) is a rare and incurable cancer. Being associated with asbestos exposure, its incidence is increasing in many industrialized countries and it will soon become a relevant issue in developing areas where this silicate is still diffuse. Molecular bases of this disease remain unknown, representing the most relevant limitation to the development of MPM targeting strategies.

New perspectives that integrate functional approaches to omics profiles are needed in order to move forward in the molecular characterization of this disease.

Mila Gugnoni, Federica Torricelli, Gloria Manzotti, Francesca Reggiani, Emanuele Vitale, Benedetta Donati, Veronica Manicardi, Elisa Salviato

Characterization of non-genetic vulnerabilities in MPM: new potential pharmacological strategies

MPM escapes the classical genetic model of cancer evolution, lacking a distinctive asbestos-associated genetic fingerprint. Using a multilayered analysis based on a functional genome-wide CRISPR/Cas9 screening integrated with patients molecular and clinical data we identified new non-genetic vulnerabilities of MPM, among which a core of chromatin organizers. Our aim is to provide an in depth characterization of their molecular mechanisms and to design innovative strategies to target their function in MPM

Long non coding RNA e MPM: non canonical strategies for surviving stress

Long non-coding RNAs (lncRNAs) are emerging as relevant molecular determinant in cancer. To map the lncRNA landscape in MPM and their functional contribution to this disease we performed an integrated analysis based on the correlation of transcriptional profiles and patients’ clinical data. Among the most interesting lncRNAs we identified linc00941 and showed how this lncRNA support MPM survival by cooperating to the regulation of protein synthesis initiation.

Mapping the immune landscape of MPM

MPM is a heterogeneous disease, in which spatial organization and local cell-cell communication represent relevant determinants. We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM organization and to reconstruct the spatial topology of MPM cells interactions. We observed the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support MPM progression. Starting from these data we are currently using the most up to date omics analysis to reconstruct the dynamic interplay between MPM cells and immune system. In parallel, using ex vivo patients samples we are deriving 3D ex vivo models to functionally reconstruct these interactions and develop strategies to interfere with the immune silencing signals. Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, our aim is to open new perspectives to improve the use of immunotherapy in this disease.