Experimental Oncology

The Department of Experimental Oncology (DOS) is branched into 10 Research Units endowed with different autonomy degrees: 3 Complex Units; 5 Simple Department Units; 2 Simple Units under sovereignty of Complex Units.  

The actual total amount of human resources in DOS is 161 units (61% non-permanent positions).  

The research carried out by DOS in collaboration with Clinical Departments aims to develop knowledge and insights in the following areas:  

1. precision prevention, which takes in consideration individuals’ differences in lifestyle, environment and biology, 
2. risk identification, screening and early diagnosis in healthy individuals, integrating biomic and radiomic technologies with artificial intelligence approaches,  
3. precision medicine for personalized patient care, 
4. sensitivity-resistance to therapies,  
5. survival and quality of life. 

By institutional ‘mission’, each Unit of the Research Department, albeit with their own expertise and specific skills, is called to participate in joint activities of multidisciplinary and transversal oncology research within which basic research can enhance and provide the best translational research approach. 

These research projects, which arise from clinical unmet needs and/or original experimental observations, are implemented in laboratories appropriately, utilizing clinical samples of patients and ad hoc pre-clinical experimental models such as homo-heterotypic cell cultures, 3D organoid-structures, in vivo models (xenografts, xenopatients, transgenic models) for the studied malignancies. The observations generated return to the clinician, with a bi-directional approach between patient and the research laboratory. This trend will allow pre-clinical research results to be transferred into current clinical practice. 

The activities carried out in the Experimental Oncology Department can be grouped in 3 main research areas: 

• BIOMICS: Genomic-epigenetic-metabolic-immune signatures and biomarkers of risk, diagnosis, prognosis, response prediction  
• IMMUNOMICS: Molecular and translational immunology, Imunobiology, Immunotherapy  
• PHARMACOMICS: Sensitivity and Resistance to Therapies, combination drug development, drug targets 

Cancer Research activities exploited in DOS cover most of the hallmarks and enabling characteristics of cancer, as exemplifies below making use of a master figure released by Hanahan et al in 2022. 

The apparent overlap of several Units on the same research areas can be well explained by the large variety of cancer types studied in our Department including: hematological tumors (leukemia, lymphoma), the majority of solid tumors of the adults (breast, head & neck, thyroid, lung, colon, ovary, prostate, melanoma, sarcomas) and pediatric cancers (brain, sarcomas, kidney). All of them require different experimental approaches and activities, technologies, expertise. The reason of such cancers heterogeneity is linked to the large demand coming from our clinicians who try to answer to urgent clinical needs in the laboratory setting, searching collaboration with the Researchers of our Department in a view of multidisciplinary research and teams in line with the institutional mission of our comprehensive cancer center (IRCCS). 

Description of Research Activities Across the Units 

Molecular Immunology (SC1) 

The Unit focuses on deciphering the intricate interaction that tumor cells establish with the immune system, the extracellular matrix, and other stromal cells during the different stages of cancer development. We study the reciprocal communication between these actors in the tumor microenvironment, as well as in primary and secondary lymphoid organs, which may sense and adapt hematopoietic responses to the neoplastic conditions, even in early phases of tumor development. The use of preclinical mouse models (knockout, conditional and transgenic) of both solid and hematological malignancies, as well as corresponding human clinical samples, allows a “bench-to-bed and backward” research approach with the dual goal of answering clinical issues and identifying new molecular mechanisms. 

Microenvironment & Biomarkers of Solid Tumors (SS1) 

SS1’s mission is focused on dissecting the role of tumor cells and their microenvironment (TME) in tumorigenesis, progression/metastasis and therapy response of breast, gastrointestinal, lung and ovarian cancers by basic and translational/clinical approaches. The research lines include the study of: resistance mechanisms to HER2-targeted treatments and chemotherapy in breast and gastrointestinal carcinomas related to tumor cells, TME and host; microRNAs involved in DNA repair regulation and TME remodeling; tumor/adipocyte crosstalk in breast carcinoma progression; lung/breast microbiota as prognostic marker and novel therapeutic target; and identification of novel biomarkers of early diagnosis and predictive of prognosis/responsiveness to neoadjuvant treatments. 

Epigenomics  & Biomarkers of Solid Tumors ( SC2) 

The scientific activity of the unit is committed to lung cancer (LC), investigating LC pathogenesis, its interaction with the microenvironment, the development of biomarkers for early diagnosis and identification of novel therapies by using an integrated approach that combines cytogenetics, molecular biology, cell biology, immunology, pharmacology and ad hoc mouse models.  

Primary activities of the Unit are: i) biomolecular characterization and mechanisms underlying lung carcinogenesis; ii) cellular subpopulations with high tumorigenic and metastatic potential iii) pulmonary stromal microenvironment; iv) innovative experimental models; v) molecular tests on circulating biomarkers to be implemented in clinical trials for screening, early diagnosis  and response to immune checkpoint inhibitors. 

Molecular Epigenomics Unit (SS2) 

The main research areas of the Unit include colorectal cancer classification using “omics” studies to identify minimally invasive (liquid biopsy) tumor-related biomarkers for early diagnosis and/or prognosis, while also contributing to a deeper understanding of the molecular pathogenesis of the disease. The unit's interests have recently expanded to the development of 3D-Organoid models generated from colorectal cancer, peritoneal diseases and corresponding normal tissues, to be used to investigate results from “omics” analyses and develop new therapeutic approaches. Engineered 3D models are also developed in which organoids are grown on natural scaffolds to integrate key features of tumor cells and the surrounding microenvironment. 

Molecular Pharmacology (SC3) 

The Unit exploits translatable preclinical models (patient-derived xenografts, orthotopic xenografts, 3D cultures) to i) validate novel therapeutic targets and resistance mechanisms identified through the multi-dimensional characterization of human tumors; ii) develop novel therapeutic strategies, based on chemotherapeutics and targeted agents matching molecular alterations characterizing specific tumor histologies or groups of tumors with similar molecular alterations, with the ultimate aim of informing the design of “biology-driven” clinical trials; iii) identify and validate novel biomarkers of tumor aggressiveness and response to anti-cancer drugs; iv) develop novel systems for the delivery of drugs and therapeutic nucleic acids. 

Translational  Immunology (SD1) 

We focus on studying interactions between tumor and the immune system in human setting, through platforms integrating cellular and molecular biology, relying on high resolution flow cytometry, transcriptional and epigenetic profiling, secretome and metabolome assessment, and new immunomodulating nanotechnologies. Globally our research is finalized to identify tools for the comprehensive assessment of local and systemic tumor immunity, to discover novel predictive/prognostic biomarkers for guiding personalized treatment and therapeutic choice. Further hallmark of the team is the commitment to translate key findings into clinical practise, by developing off-the-shelf assays, performing prospective validation studies and defining innovative immunotherapeutics in Oncology. 

Integrated Biology of Rare Tumors (SD2) 

In cancer patients, disease recurrence and development of resistance to treatment are unmet clinical needs particularly when dealing with rare diseases whose studies may be affected by the low number of available cases. Through basic and translational studies we aim to gain insights in the biological and molecular characterization of patients, to favor a personalized therapeutic approach for a prognostic improvement. 

Our projects involve a close collaboration with disease-oriented clinicians and the integration of data derived from human tissue analysis, multiomics data processing, functional studies in preclinical in-vitro and in vivo models focusing on: Thyroid, Ovarian, Head and neck cancers and Pediatric brain tumors. 

Research in Nutrition and Metabolomics (SD3) 

The Unit aims to integrate the epidemiological data on diet and cancer with metabolomics to improve the knowledge of cancer biological processes and promote the development of personalized treatments useful for prevention and clinical practice. The unit includes a fully equipped laboratory (NUMELAB) with expertise to perform analyzes in high-resolution mass spectrometry, including mass spectrometry-based breath analysis for a non-invasive early diagnosis of head/neck/breast cancers, and immunometric assays on complex biological matrices.  

The research activity consists of dietary intervention trials, design of adjuvant lifestyle treatment for patients, lipidomic/metabolomic analyses and mass spectrometry-based breath analysis. 

Predictive Medicine & Molecular Basis of Genetic Risk (SD4) 

This research unit is devoted to the identification and characterization of constitutional genetic factors associated with hereditary susceptibility to cancer and, limitedly to pediatric diseases, of somatic genetic alterations contributing to tumor progression and affecting response to therapies.  

Primarily investigated diseases are breast cancer and Wilms tumor. 

Main research areas are: 

1. To define the clinical relevance (in relation to cancer risk) of rare germline alleles of breast cancer predisposition genes. 
2. To elucidate the biological relevance of common risk alleles contributing to breast cancer susceptibility through a polygenic model of inheritance.  
3. To identify and/or validate molecular markers for better treatment stratification of patients affected with Wilms tumor. 

Animal House (SD5) 

The mission of the animal house facility is to support pre-clinical research activities in oncology, implementing an animal experimentation conducted in an ethical manner, using appropriate methodologies to obtain scientifically valid and reproducible results. In vivo research pays particular attention to the concepts of replacement, reduction of the animals used as well as the refinement of procedures, the optimization of which translates into the welfare of the animals and promotes good scientific practice. 

The facility is also accredited for the breeding of genetically modified animals used as model organism for studying tumor pathologies, with the aim to identify and characterize the molecular mechanisms underlying the onset and the progression of these tumors, and to test new pharmacological treatments.