Development of a new therapeutic tool against malignant mesothelioma

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Malignant mesothelioma (MM) is a very aggressive tumor and, currently, there are no effective chemotherapeutic drugs or molecular-target reagents against this fatal disease. In this project, we performed experiments to develop a new therapeutic modality against MM. Since MM shows frequent inactivation of p16INK4a tumor suppressor gene, we employed a functional peptide which is permeable through the cell membrane and restores p16 function. We found that this peptide induced apoptosis of MM cells very effectively and specifically, which seemed promising to be a new therapeutic tool. Furthermore, we also analyzed YAP oncogene product, which is constitutively activated and leads to more malignant phenotypes of MM cells. We clarified which members of TEAD family transcription factors, YAP binding partners, were important in deregulated MM cell proliferation. These findings were very indicative to develop a new strategy to regulate YAP protein as a therapeutic modality of MM.