Dr. Carbone, Director of the Prostate Cancer Biology laboratory, is a medical researcher focused on basic and translational research. She obtained MD degree in 1983 (magna cum laude) and completed clinical residency in 1987 (magna cum laude) at the University of Naples Medical School. From 1988, she was research fellow at Wake Forest University Medical Centre (Winston-Salem, NC, USA) in the Department of Physiology and Pharmacology. From 1994, she was post-doctoral research fellow and from 2001, Research Assistant Professor in the Laboratory of Cancer Genomics at the Hollings Cancer Centre of the Medical University of South Carolina (MUSC), Charleston, USA. In 2003 she joined the IOR in Bellinzona, as Group Leader of the Prostate Cancer Biology laboratory. Dr. Carbone is a member of the AACR, WCR, NCCR network, EAU and EBU-EAU. She has received continuous funding from Swiss National Science Foundation (SNSF), Oncosuisse (Swiss Cancer League, KLS), Swiss Bridge and Fondazione Ticinese per la Ricerca sul Cancro. Her group has a long-term interest in ETS transcription factors and their role in prostate cancer progression. Current topics of the research include transcriptional and epigenetic reprogramming induced by ETS factors. A novel area of research includes the study of extracellular vescicles/exosomes as oncogenic mediators of prostate cancer progression and as biomarkers in liquid biopsy.
Novel in vivo models to study the role of the ETS factor ESE3/EHF The team has been the first to point that ESE3/EHF (member of the sub-family of epithelial-specific ETS transcription factors, endogenously expressed in many epithelial tissues) is involved in prostate epithelial cell differentiation, transcriptional and phenotypic reprogramming, and that its loss leads to acquisition of stem-like and tumorigenic properties. A recent accomplishment of the group is the production of the first mouse model with prostate conditional knockout of ESE3/EHF. Molecular and functional characterization of this model is ongoing in the laboratory by integrating molecular studies with multiomic approaches.
Epigenetics and progression of ERG fusion positive tumors
The laboratory focuses on gene fusions involving the ETS transcription factor ERG (TMPRSS2:ERG), very frequent in prostate cancer. An important notion recently emerged is that ERG requires the cooperation of other transcription factors and epigenetic regulators to fully exert its oncogenic potential. The team contributed to this new paradigm providing compelling evidence of a novel molecular mechanism of ERG activation based on EZH2-induced ERG methylation. The group defined the relevance of this post-translational modification and its impact in driving disease evolution towards the metastatic and castration resistant status. These studies are also providing new insights for developing more effective therapies for aggressive prostate tumors.
Circulating exosomes: novel biomarkers in prostate cancer
The group reported that ETS transcription factors directly control a network of microRNAs. This analysis led to discovery of a novel axis involving loss of ESE3/EHF and upregulation of a microRNA, miR-424, leading to increased stemness and tumorigenic potential of prostate cancer cells. Moreover, the group found that miR-424 is released by tumor cells in small extracellular vesicles or exosomes circulating in blood of patients with more advanced and aggressive prostate cancers. Exosomes are relevant means for transferring signals across cells and can facilitate the propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Exosomes containing miR-424 induced stem-like traits and tumor-initiating properties in prostate epithelial cells and their administration by intravenous injection, mimicking their blood circulation in patients, promoted tumor growth in mouse xenograft models. These data identify a novel mechanism that promotes prostate cancer progression through exosome-mediated transfer of potent oncogenic effectors like miR-424 to other cells in the surrounding microenvironment or at distant metastatic sites. These findings might suggest novel approaches for the management and treatment of prostate cancer.