Ph.D. Program in Biomedical Sciences and Oncology

The relevance of the research lines pursued by the Pathology Unit derives from the integrative and multimodal analysis of tumor and patients’ specific characteristics, that lead to the definition and clinical validation of novel diagnostic, prognostic and predictive biomarkers; therefore, the research activity has as a primary aim to improve clinical strategies by identifying novel markers helping to tailor the best therapeutic approach for each individual patient or tumor type, thus depicting detailed molecular signatures associated to patients’ prognosis and therapy-specific outcome.

In the field of thoracic oncology, our group contributed individually or as a partner of multicentric studies to establish the optimal panel of immunohistochemical markers to depict tumor histology in non-small cell lung cancer even in small cytological/bioptical samples, with the discovery and validation also of novel tools, such as the squamous histotype-specific marker desmocollin-3 for non-small cell lung cancer. Moreover, several studies on the controversial and poorly characterized group of pulmonary “large cell carcinoma” and on pleural mesothelioma contributed to depict their profile of expression of molecular markers associated to response to chemotherapy, with the direct consequence of driving oncologists decisional approach in terms of chemotherapeutic strategies for patients affected by these special tumor types. As to concern endocrine pathology, several previous and current research projects on thyroid malignancies were focused on the validation of markers at both immunohistochemical or molecular levels with strong impact in terms of diagnostic usefulness in discriminating benign vs malignant lesions in cytological fine-needle aspiration samples. Among these, galectin-3 has been already validated in a large prospective multicentric trial and is diagnostic standard in several centers world-wide. In adrenal cancer, our group largely contributed, with several seminal studies, to the definition of its diagnostic criteria, to the pathological characterization of special variants, to the discovery of potential novel prognostic parameters and to the identification of molecular signatures associated to specific profiles of therapeutic responsiveness. Finally, for neuroendocrine tumors, our group contributed to the characterization of peptide receptors with well-established (namely somatostatin receptors, with the definition of an Immunohistochemical scoring system of diagnostic value widely referenced in the literature) or potential (ghrelin-axis receptors) clinical relevance. Moreover, large series of neuroendocrine tumors (medullary thyroid cancer and lung carcinoids) have been largely explored for the expression profile of molecules acting in relevant intracellular pathways (such as the mTOR pathway) that are strong candidates as targets for novel drugs recently introduced in the market and already tested in large clinical trials.

For the next years, our Unit aims to increase in the different fields of research the knowledge on mechanisms of cancer growth and therapeutic respionsiveness prediction by using novel high-throughput technologies, including next generation sequencing, and expanding in vitro models to understand the mechanisms of drug responsiveness and resistance or functionally characterize newly recognized molecular defects. The ongoing research in lung cancer is currently focused on the molecular characterization of special forms of non small cell lung cancer  (special variants, such as mucinous adenocarcinomas, or tumors with special clinical characteristics, such as early age onset or advanced-stage recurrent disease). In pleural mesothelioma, studies are performed to discover and validate novel molecular pathways or genes that are significantly associated to disease predisposition, early diagnosis or of prognostic/predictive role. As to concern thyroid malignancies, current studies are focused on the diagnostic validation of molecular tests, such as the mutational analysis of thyroid cancer relevant genes BRAF and RAS, and on the molecular characterization of special forms of clinically aggressive thyroid cancers, which our group previously largely contributed to define and pathologically characterize. In adrenal cancer, a multimodal research approach is planned to integrate molecular and pathological signatures to specific profiles of therapeutic responsiveness. Ongoing research in neuroendocrine tumors is mostly focused on the definition of molecular classes of neoplasms of different sites with potentially different biological and clinical behaviors. Finally, a specific project is planned to discover the molecular mechanisms that drive basal or acquired neuroendocrine differentiation, with special reference to hormonally treated prostate cancer.