Manipulation of senescence pathways for cancer therapy: from experimental models to clinic

Senescence is an irreversible cell growth arrest which opposes tumor formation  by blocking tumor proliferation and triggering an immune tumor clearance. Aim of this Score project is to identify novel pro-senescence compounds for cancer therapy. We have recently developed a screening platform for the identification of novel pro-senescence compounds (PICS assay) by using  the Pten loss induced cellular senescence model. Compounds will be selected by taking advantage of bioinformatics, chemogenomic and drug repositioning approaches and will be screened in the PICS assay and in the Pten mouse model. Identified leads will be validated in human cancer cell lines and quiescent cancer stem cells. This study model will lead to the appropriate development of pro-senescence compounds from in vitro to the pre-clinical and clinical phase.