Abstract A15: New treatment opportunities by in vivo and in vitro screening approaches in melanoma

Treatment of metastatic melanoma has been recently revolutionized by the use of targeted and immune inhibitors, though efficiently working only in a fraction of patients. Adverse effects still represent major challenges, as well as the rapid development of drug resistance upon treatment, thus suggesting that it is of utmost importance to elucidate additional molecular pathways and targets to better understand the biology of this tumor. In vivo RNAi screens done in patient-derived xenografts (PDXs) that fully phenocopy the original tumor of the patient represent a powerful tool to identify new putative essential and druggable candidates, and to repurpose drugs already approved for other indications. To this end we have recently generated a platform of melanoma PDXs with which we can recapitulate both melanoma growth and metastasization. We have performed in vivo shRNA screens, where we have found numerous and patient-specific epigenetic genes essential for tumor growth in vivo. With this platform, we have isolated novel frailties whose depletion favors cell senescence. Preliminary data using shRNA libraries of actionable genes for which drugs are already available suggest that specific drugs can be repurposed for melanoma treatment. We have proved that this approach can work in vivo, and we propose to convert it in an in vitro assay to rapidly translate new discoveries to the patient. Note: This abstract was not presented at the conference. Citation Format: Federica Marocchi, Letizia Granieri, Fiorenza Lotti, Fernando Palluzzi, Jole Costanza, Laura Riva, Daniela Bossi, Luisa Lanfrancone. New treatment opportunities by in vivo and in vitro screening approaches in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A15.