Research Group

Piscuoglio Group

Precision Medicine Lab

Piscuoglio Group

Salvatore Piscuoglio

Group Leader

Piscuoglio’s lab aims to accelerate the application of precision medicine in cancer – identifying clinically relevant predictive biomarkers and novel drug targets – by leveraging emerging technologies such as ex vivo 3D models in combination with multiomics profiling and artificial intelligence, fostering strategic partnerships and conducting translational research.

The Challenge

Human cancers are underpinned by molecular aberrations and show remarkable molecular and clinical heterogeneity. This variability means that standard treatments often fail to be effective for all patients, leading to suboptimal outcomes and adverse effects. The complexity is further compounded by the presence of diverse genetic aberrations that drive carcinogenesis, making it imperative to identify specific biomarkers and therapeutic targets unique to each cancer type and subtype. Our research is crucial in tackling these issues, as we strive to develop personalized therapeutic strategies that enhance treatment efficacy, improve survival rates, and minimize side effects. By focusing on precision medicine and leveraging advanced technologies and collaborative efforts, our lab seeks to transform the clinical management of cancer, offering hope for more tailored and effective treatments for patients.

Main research areas

Exploiting cancer vulnerabilities

The discovery and development of innovative drugs have transformed the cancer treatment landscape, leading to significant survival improvements in many cancer types. However, limited efficacy of standard of care, acquired and/or intrinsic drug resistance hampers effective treatment of many cancer types, and the identification and validation of novel drug targets remain one of the major challenges in anticancer drug discovery. To identify new therapeutic options for cancer patients, our lab uses various high-throughput multiomics technologies, such as genomics, transcriptomics, (phospho)proteomics, and metabolomics, to pinpoint genetic and signaling pathways that are aberrant in cancer cells and can be exploited for treatment.

From living tumor biobank to tumor organoids

To enable drug profiling in ex vivo models representative of the molecular diversity of cancers, our laboratory has teamed up with various surgery departments to establish a living biobank composed of patient-derived organoids (PDOs) matched with immune, stromal, and endothelial cells. To better mimic the pathophysiological microenvironment of cancer, we have generated 3D models using the different type of cells isolated from the tissue specimen (assembloids) or using organ-on-chip to maintain the tumor tissue architecture.

Precision drug screening

These tumor models are being used for multi-omics profiling, large-scale drug screening and toxicity studies, and the discovery of targetable cellular interactions. Using cancer-specific models 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.

Selected publications

Harter MF
Nat Biomed Eng
Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids.
Gallon J
Cancer Res
DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations.
Srivatsa S
Nat Commun
Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens.
Rodriguez-Calero A
Nat Commun
Alterations in homologous recombination repair genes in prostate cancer brain metastases.
Bianco G
Commun Biol
GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.
Gallon J
Mol Oncol
Epigenetic priming in chronic liver disease impacts the transcriptional and genetic landscapes of hepatocellular carcinoma.
Marinucci M
Front Oncol
Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues.
Montazeri H
Nucleic Acids Res
Systematic identification of novel cancer genes through analysis of deep shRNA perturbation screens.
Taha-Mehlitz S
Theranostics
Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis.
Cyrta J
Nat Commun
Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity.
Ng CKY
Ann Oncol
Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.
Piscuoglio S
Clin Cancer Res
The Genomic Landscape of Male Breast Cancers.
Piscuoglio S
J Pathol
Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression.
Weinreb I
Nat Genet
Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands.

Group members

Piscuoglio Group
Reha Akpinar

PhD student

Piscuoglio Group
Miriam Cieri

PhD student

Piscuoglio Group
Federico Donà

Postdoc fellow

Piscuoglio Group
Barbara Durante

Postdoc fellow

Piscuoglio Group
Silvia Erratico

Technician

Piscuoglio Group
Silvia Incalcaterra

Technician

Piscuoglio Group
Karina Koczberska

Fellow

Piscuoglio Group
Melania Lazzari

PhD student

Piscuoglio Group
Carola Maria Morell

Postdoc fellow

Piscuoglio Group
Giulia Milardi

Postdoc fellow

Piscuoglio Group
Umberto Miracca

Technician

Piscuoglio Group
Salvatore Piscuoglio

Group Leader