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Cancer: personalized prevention and a new mutational model

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Cancer: personalized prevention and a new mutational model

The oncologist as a ‘Sherlock Holmes’ of the human body who, instead of a magnifying glass, uses the new tools of molecular pathology to search not only for genes or molecular targets, to be targeted with targeted anti-cancer therapies, but also for the molecular alterations that they allow the identification of population groups at risk for prevention. This is the precision oncology thanks to which today it is possible to aim at treatments but also at personalized cancer prevention. The new frontiers are outlined today in Rome at La Sapienza University at the “World Health Summit Regional Meeting – Europe”, in the session dedicated to precision oncology, moderated by Paolo Marchetti (Scientific Director IDI IRCCS of Rome, Full Professor of Oncology at La Sapienza University of Rome and President of the Foundation for Personalized Medicine) and by Khay-Guan Yeoh (Professor of Medicine at the University of Singapore). The purpose of the “World Health Summit Regional Meeting – Europe”, which is part of the “World Health Summit” which takes place every year at the end of October in Berlin, is to study innovative elements, recommendations to be offered for the evaluation of political and academic authorities. These are projects of clinical application to overcome the inequalities still present in health systems and in access to therapies.

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Personalize prevention

In the meeting, organized every year by the Alliance of Academic and Research Centers (M8 Alliance of Academic Health Centers, Universities and National Academies), topics of great importance are addressed, ranging from vaccines to public health management systems, to metabolic syndromes to chronic diseases, up to new technologies and personalized medicine. But in what sense does prevention become personalized? “Because it can be based on precision medicine models, through the identification of specific genomic determinants linked to an increased risk of developing cancer”, replies Marchetti.

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Only one test to detect 4 female tumors

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Mutations in the Brca gene

This includes a series of interventions to identify the tumor at an early stage or to avoid the onset of the disease. “For example – explain Paolo Marchetti and Stefania Boccia, professor of Hygiene, Preventive Medicine and Public Health at the Catholic University of the Sacred Heart of Rome – women with a mutation of the BRCA gene, which represents a risk factor for breast cancer, may be offered more frequent breast screening programs, which are part of secondary prevention, or treatment with aromatase inhibitors or antiestrogens, still in clinical trials, to enhance primary prevention. In this way we can save more lives and guarantee savings for the health system ”.

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The role of molecular pathology

In short, molecular pathology is a cornerstone of precision oncology. “The genetic mutation – continues Marchetti – can no longer represent the solution to the problem. It is necessary to learn to study not only the single alterations but the overall modifications of the cellular signaling pathways. Thus the molecular pathologist can provide the clinician with information that is decisive for the choice of therapy. For example, a patient with a high mutational burden, theoretically a candidate for immunotherapy, must be referred to another treatment in the presence of a mutation that blocks the response to immunotherapy ”.

From the histological to the mutational model

The so-called histological model that has long governed clinical research in oncology, regulatory decisions and clinical practice is now joined by the molecular model. “In this approach, the starting point is represented by the organ from which the disease originates, followed by the histological examination, the identification of any molecular alterations and the choice of the drug, through a path of selection of patients who they are more likely to respond to treatment, ”adds the oncologist. The histological model has been superseded by the agnostic one, in which oncological therapies are chosen independently of the tumor site on the basis of specific genomic alterations or particular molecular aspects present in different tumors, which represent the cellular target. “And today the new model is the ‘mutational’ one in which all the alterations undergone by the organism must be considered, also including the microbiota, that is the set of billions of billions of microorganisms that live in the body providing essential support to our life “.

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