Research interests

Cancer of unknown primary (CUP) is an elusive clinical and pathologic entity comprising metastatic tumors that are diagnosed in the absence of a clinically detectable primary lesion. CUPs are characterized by (i) an early and unpredictable metastatic pattern, and (ii) an undifferentiated phenotype not referable to any organ/tissue of origin. CUPs are relatively rare (3- 5%) but, owing to their aggressiveness and lack of therapeutic rationale, are an unsolved clinical problem. CUPs represent a quintessential metastatic disease, whose understanding can shed light on the largely obscure genetic, molecular and biological principles governing cell dissemination and homing throughout the organism in all cancer subtypes. In CUPs the invasive and undifferentiated phenotypes -distinctive of 'cancer stem cells'- are tightly associated and possibly concomitantly regulated, and the underlying genetic/molecular mechanisms might represent the Achille's heel of metastasis. By a robust, multi-disciplinary and integrated translational platform, we intend to (i) deeply characterize the genomic landscape of CUPs, to discover case-specific and common genetic dependencies and functional vulnerabilities; (ii) characterize the molecular basis sustaining the undifferentiated, stem and invasive traits shared by CUPs; (iii) challenge potential 'drivers', emerged from genetic and functional annotations, as targets for personalized medicine. These top-down efforts are complemented by hypothesis-driven, bottom-up approaches, leveraging on the long- standing experience of the research team in the functional characterization of MET oncogene and Semaphorin/Plexin family as drivers of invasive growth, angiogenesis and metastasis, as well as regulators of the cancer stem cell phenotype.