Salvatore Piscuoglio

Cancer is a complex and heterogeneous disease that arises from alterations in multiple genes and pathways, making it challenging to identify effective treatments. My research focuses on defining novel “cancer genes”, clinically relevant predictive biomarkers of response/ resistance to therapy and discovering novel drug targets using a multi-modality approach, incorporating computational predictions, multi-omics profiling with ex-vivo drug profiling. To identify new therapeutic options for cancer patients, my group uses various high-throughput technologies, such as genomics, transcriptomics, proteomics, and metabolomics, to pinpoint genetic and biochemical pathways that are aberrant in cancer cells. These approaches enable the identification of genes and molecules that are involved in key dysregulated cellular processes in cancer, such as cell proliferation, differentiation, and survival. Potential targets are then characterized using a variety of cell-based assays, in vitro and in vivo models, and structural biology techniques. Finally, using cancer-specific patient-derived organoids or tumor fragments, we test compounds such as small molecule inhibitors, monoclonal antibodies, and gene therapies designed to target specific molecular pathways or processes essential for cancer cell survival and proliferation, thereby enabling the selective killing of cancer cells.

1. Gallon J, Rodriguez-Calero A, Benjak A, Akhoundova D, Maletti S, Amstutz U, Hewer E, Genitsch V, Fleischmann A, Rushing EJ, Grobholz R, Fischer I, Jochum W, Cathomas G, Osunkoya AO, Bubendorf L, Moch H, Thalmann G, Feng FY, Gillessen S, Ng CKY, Rubin MA, Piscuoglio S. DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations. Cancer Res. 2023 Apr 14;83(8):1203-1213.
2. Srivatsa S, Montazeri H, Bianco G, Coto-Llerena M, Marinucci M, Ng CKY, Piscuoglio S*, Beerenwinkel N.* Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens. Nat Commun. 2022 Dec 14;13(1):7748.
3. Bianco G, Coto-Llerena M, Gallon J, Kancherla V, Taha-Mehlitz S, Marinucci M, Konantz M, Srivatsa S, Montazeri H, Panebianco F, Tirunagaru VG, De Menna M, Paradiso V, Ercan C, Dahmani A, Montaudon E, Beerenwinkel N, Kruithof-de Julio M, Terracciano LM, Lengerke C, Jeselsohn RM, Doebele RC, Bidard FC, Marangoni E, Ng CKY, Piscuoglio S. GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers. Commun Biol. 2022 Apr 19;5(1):373.
4. Taha-Mehlitz S, Bianco G, Coto-Llerena M, Kancherla V, Bantug GR, Gallon J, Ercan C, Panebianco F, Eppenberger-Castori S, von Strauss M, Staubli S, Bolli M, Peterli R, Matter MS, Terracciano LM, von Flüe M, Ng CKY, Soysal SD, Kollmar O, Piscuoglio S. Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis. Theranostics. 2021 Feb 15;11(9):4011-4029.
5. Weinreb I*, Piscuoglio S*, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, Harding NJ, Alfaro J, Chu KC, Viale A, Fusco N, da Cruz Paula A, Marchio C, Sakr RA, Lim R, Thompson LD, Chiosea SI, Seethala RR, Skalova A, Stelow EB, Fonseca I, Assaad A, How C, Wang J, de Borja R, Chan-Seng-Yue M, Howlett CJ, Nichols AC, Wen YH, Katabi N, Buchner N, Mullen L, Kislinger T, Wouters BG, Liu FF, Norton L, McPherson JD, Rubin BP, Clarke BA, Weigelt B, Boutros PC, Reis-Filho JS. Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands. Nat Genet. 2014 Nov;46(11):1166-9.