To favor translational research, the department has launched a number of top-down scientific programs whose specific aim is to create technological platforms for translational science and foster the interaction between basic scientists and clinicians, on specific research projects. They include: i) Clinical Genomics Program, ii) Novel Biomarkers Program, iii) Novel Diagnostics Program, iv) Smartfood Program. In addition, our Department is fully committed to gender equality, with the Women in Science Project, and deeply involved in Ethical, Legal and Societal Issues, through the long standing expertise in bioethics as well as in Science and Technology Studies-based analysis of contemporary biomedicine, with the Science in Society Project.
Clinical Genomics Program
Pier Giuseppe Pelicci
The Clinical Genomic (ClinGen) lab at IEO aims at maximizing genomic information to improve patients’ management, continuously translating new genomic discoveries into suitable biomarkers. The lab acts as a referral center for the IEO genetics service by providing diagnostic-grade sequencing of germline cancer risk-associated variants. With a throughput of ~500 subjects a year, the lab is among the largest in Italy. The lab conducts numerous sequencing-based research projects and coordinates the efforts of the Genomics Working Group of the Alleanza Contro il Cancro (ACC) network, a consortium of >20 comprehensive cancer centres in Italy. The lab designed and validated high-throughput (200-400 genes) and low cost (500-700E) custom panels for the analyses of the Actionable Genome, including: -Multigene germline risk panels (26-96 risk-associated genes), routinely used for cancer genetics and tested in prospective trials on sporadic ovarian and triple-negative cancers (n=500 over 2 years) -Lung cancer panel, in a prospective multicentric national trial (n=1000) -PanCancer panel (GerSom), tested in multiple muticentric trials -Clonal Hematopoiesis (CHIP) panel to monitor clonal evolution of hematological neoplasms -Myeloid neoplasms panel (MyeloPanel), pre-diagnostic predisposition and somatic actionability of hematological neoplasms. Additional interests in the lab are: -Identification of novel cancer-predisposing variants -Implementation of novel technologies (liquid biopsies, long-read sequencing, radiogenomics) for disease monitoring -Development of clinics-centred bioinformatic pipelines.
New Drugs Program
Main goals of the Program is to guarantee quick access to innovation to IEO patients through: • Commitment to provide exciting new therapies from the very earliest stages, when they first enter the clinic • Accelerated activation and conduction of high quality early clinical trials (phase I and early phase II) • Promotion of innovative early clinical-trials linked to molecular screenings/analyses • The identification of new drugs • Promotion of innovative studies in preclinical models/on patient samples to test new therapies and identify new targets/biomarkers. In our program, our doctors and scientists work together to expand our drug development initiatives and our patients benefit from close communication with their healthcare team. To achieve these goals, we aim to further strengthen the interactions among the two “souls” of our Institute (basic research and clinical research). Our mode of work therefore starts with questions/hypotheses that have roots in fundamental research, and at the same time reflect an immediate clinical question/patient need. Deepening our mechanistical understanding of those questions will therefore translate into a “product” (new markers, new treatments) that will be tested clinically, and -in case of success of the clinical studies- can result in a ready benefit for our patients. At present, our work is focusing on identifying new mechanisms of resistance to therapy, including new drugs that recently entered clinical use. We hope to overcome these mechanisms with a combination of multiple drugs, and have already achieved preclinical results supporting this line of research.
Novel Diagnostics Program
Pier Paolo Di Fiore
The application of ‘omics’ technologies to cancer has revealed the full extent of the molecular heterogeneity of this disease and brought into question the ‘one-size-fits-all’ approach to therapy. Our challenge now is to exploit the wealth of molecular knowledge stemming from ‘omics’ projects, to develop innovative clinical tools for the personalized management of cancer. The Novel Diagnostics Program strives to do just this through projects aimed at mining profiles generated in the lab to identify and, eventually, validate novel tumor markers for the diagnosis, prognosis, stratification, and therapy response prediction in cancer patients.The program is equipped with cutting-edge technological platforms and experienced research staff dedicated to the screening and clinical validation of candidate markers in large patient cohorts, statistical analyses to develop cancer risk models, validation studies in pre-clinical models, and assay optimization to increase transferability to the clinic. Close ties between the Program and the IEO clinical divisions ensure that the Program addresses the most pressing unmet clinical needs, and also facilitate the clinical development of novel tests by allowing access to patient cohorts and the setup of clinical trials. Current activities of the Novel Diagnostics Program are focused on the identification and validation of biomarkers for diagnostic, prognostic and therapeutic stratification in breast, prostate, bladder and lung cancers, with a special focus on the characterization and clinical validation of biomarkers based on the biology of cancer stem cells.
Pier Giuseppe Pelicci
Epidemiological and experimental evidences demonstrate that only a small proportion of cancers are inherited; environmental factors are the most important cause of genetic modification. These factors include food poisons such as mycotoxins or alcohol as well as smoking, infectious agents, radiation, drugs, industrial chemicals and pollutants. Thus, habits (including a healthy diet) aimed to minimize the exposure to these carcinogens are known to protect from tumorigenic mutations. More recently some dietary patterns and physical activity have been demonstrated to prevent cancer and other aging associated disease, by altering the functions of specific genes (belonging to the longevity genetic pathways) and inhibiting fat accumulation, which increases cancer risk. It means that a healthy environment can stop cancer before it starts. In this context, nutrition represents an extraordinary tool to prevent cancer and other aging associated disease. The aim of our Translational Research Program Smartfood is to improve nutrition at different levels, taking advantage of our already existing network. The potential benefits of the Program include: to ameliorate the understanding on the connection between diet and lifespan; to motivate a positive behaviour change; to improve the awareness of major risk factors; to promote health and encourage an active healthy ageing; to effectively teach primary prevention strategies; to reduce health care costs; to clarify the mechanisms involved in disease susceptibility.