Hormone-Related Cancers and Stem Cell Pathobiology
|Location|| Building 13 |
Via Adamello 16, Milano
Our lab aims to understand the cellular and molecular basis of tumor heterogeneity in order to develop biology-driven approaches for the treatment of cancer patients. We are particularly interested in cancer stem cells (CSCs) and how they contribute to tumor heterogeneity and drive tumorigenesis, therapy failure and metastasis.
The CSC theory proposes that tumorigenesis can be viewed as normal tissue morphogenesis gone awry, with the formation of tumors being driven by stem-like cells that display abnormal self-renewal properties, resulting in the generation of aberrantly differentiated progenitors and an expanded heterogeneous CSC compartment.
Despite increasing evidence supporting the existence of CSCs, their exact identity in many cancers has remained elusive. By studying the molecular identity and pathobiology of CSCs, we aim to identify prognostic/predictive biomarkers for patient stratification and tailoring therapy, and novel molecular targets for personalized therapy.
This approach has been applied to breast cancer where we have developed a prognostic test, StemPrintER, based on the transcriptional profile of breast SCs (Pece S. 2019 EBioMedicine). We have also determined that loss of the tumor suppressor protein Numb in breast cancer is responsible for aberrant CSC self-renewal and tumorigenesis and correlates with poor prognosis. Notably, targeting Numb dysfunction represents a selective anti-CSC therapy for aggressive breast cancers (Tosoni D. 2017 EMBO Mol Med).
Most Relevant Publications
Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study.
Pre-clinical validation of a selective anti-cancer stem cell therapy for Numb-deficient human breast cancers.
EMBO Mol Med, 2017
The Numb/p53 circuitry couples replicative self-renewal and tumor suppression in mammary epithelial cells.
J Cell Biol, 2015
Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content.