Detailed projects description
Characterization of prostate cancer stem cells
Prostate cancer stem cells (PCSCs) are thought to have a central role in driving tumor aggressiveness, resistance to androgen-deprivation therapy, disease relapse and metastasis. However, their precise molecular and cellular identity is still unknown. Through the molecular and functional characterization of the different cell populations within primary tumor specimens and established prostate cancer cell lines, we have identified novel candidate PCSC biomarkers. We are currently investigating whether these biomarkers can identify, within the bulk tumor, cells endowed with biological traits typical of cancer stem cells: namely, unlimited self-renewal ability, tumor-initiating ability, and resistance to androgen-deprivation therapy.
From a clinical perspective, we are analyzing the prognostic value of our candidate biomarkers for prediction of biochemical recurrence and distant metastasis in a large patient cohort with complete long-term follow-up. We are also exploring the therapeutic significance of our biomarkers, particularly in relation to overcoming resistance to androgen-deprivation therapy.
Finally, we are using single cell next-generation sequencing to perform an in-depth molecular characterization of PCSCs, which could lead to the identification of a PCSC-specific signature. In parallel, we are leveraging the potential of digital pathology based on in situ single cell profiling with multiplexed immunofluorescence/immunohistochemistry and spatial in situ transcriptomics to gain detailed topological information at the single cell level, with the ultimate goal to highlight the intratumoral spatial and temporal heterogeneity typical of prostate cancer, and make inferences on tissue sociology within the prostate cancer hierarchy and on tumor-microenvironment cell-cell interactions.
Validation of prognostic and therapeutic biomarkers in bladder cancer
Bladder cancer is a major cause of cancer-related death; however, little progress has been made in its prognosis and treatment over the last decades and the burden of this disease in terms of morbidity, mortality and related healthcare costs remains high. We are tackling this issue by characterizing “driver” alterations in the urothelial stem cell compartment that could lead to the identification of novel biomarkers and molecular targets for bladder cancer.
Our group has already identified a candidate driver alteration that we are currently validating for prognostic value by interrogating cohorts of patients with muscle-invasive and non-muscle invasive disease. Our aim is to develop a prognostic/predictive clinical tool for patient stratification that allows the correct treatment to be directed to those patients most likely to benefit, while avoiding overtreatment.
To identify potential therapeutic targets, we are attempting to elucidate the mechanisms underlying the transition from non-muscle invasive to muscle-invasive bladder cancer, which is the key event in the clinical setting related to the adverse evolution of the disease. We are also investigating the upstream mechanisms responsible for the driver alteration we identified, as well as its downstream signaling consequences.