| Interview to Pierotti |
 Interview to Marco A. PierottiFondazione Irccs Istituto nazionale dei tumori Scientific Director Q: What kind of new stimulus is now strategic for your research on cancer? A: Cancer is a disease generated by alterations of the genes in our cells. It is therefore very likely that the knowledge of the structure of our genome and the beginning of our understanding of its function will provide a significant advance in our knowledge and management of cancer. In this context our interest, internationally recognized, has been developed along two main lines of investigations which are predicted to bring a significant impact on cancer-related clinical aspects: a molecular classification of cancer based on molecular abnormalities and investigations in the field of inherited tumors. Molecular taxonomy of different cancer types has shown its utility for the development of predictors for cancer progression and treatment response, is fundamental for the so-called “targeted therapy”, and ultimately provides the bases for the molecular diagnosis of cancer. However, new high-throughput technologies scanning the human genome are providing us with a vast array of results and have revealed a high and complex heterogeneity of the disease making virtually impossible to identify homogeneous subgroups showing the same genetic lesions.Q: How do you overcome this critical point? A: We will contribute to solve this problem by focusing on two “big killers”: breast cancer, which is the commonest cancer type in women, and colon cancer. Both of them have a strong psychological and social impact and constitute a relevant problem for Public Health. We propose to challenge the concept that a genetic heterogeneity could be reduced to a more homogeneous sub-grouping of different tumors of the same type from a gene expression analysis of coding and non-coding RNAs (miRNA). Expression data will be integrated together with a genome-wide gene copy number assessment (CGH) and a large scale methylation analysis to highlight relevant genetic elements not yet associated to cancer. We will also explore the possibility to highlight altered genetic mechanisms by using an in silico search of autocrine/paracrine loops involving cognate receptor/ligand pairs which will be biologically validated. Q: Have you achieved results? A: We already successfully applied the method and found new receptor/ligand pairs in ovary cancer. Our ultimate aim is to identify the key players of the molecular sub-groups in the different analyzed tumor types and to functionally validate these genetic elements that could be subsequently used to identify widely shared elements for a targeted therapy. As for the inherited cancer we have developed a multidisciplinary approach involving genetists, molecular biologists, psychologists and clinicians with different expertise following the concept of a Family Cancer Clinics. We have pioneered the field since 1995 and are currently following more than 500 Italian families affected by hereditary breast cancer (gene BRCA 1 and 2) and also a large number of families with hereditary colon cancer.
Q: Is this approach shared by many groups abroad?
A: This activity is formalized in one of the few available example of a Department of Predictive and Preventive Medicine. We want, in fact, not only to evaluate the genetic risk to develop cancer but also to provide answer to develop effective preventive, early diagnosis and eventually tailored therapy for this field of diseases.
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