Scientific Direction

Paolo Comoglio, M.D.
Full Professor, UniTo
E-mail: paolo.comoglio@ircc.it
Phone. +39.011.9933601
Fax. +39.011.962.1525

Publications
Mission and scientific coordination
The Candiolo Cancer Institute is a biomedical and clinical research center entirely devoted to the study and the treatment of cancer. Its mission is to transfer experimental preclinical information into clinical practice, through the continuous flow of knowledge from the fields of genetics, molecular and cell biology and pathology. The Institute aims to offer a significant contribution to the defeat of the disease through scientific research and clinical practice of excellence. In order to fulfill these goals, the Institute: (i) capitalizes on knowledge by conducting scientific research in oncology and – at the same time - by promoting fast transfer of knowledge to the clinical practice; (ii) provides assistance in cancer prevention, including the identification of genetic risk factors; (iii) performs diagnostic studies, using state-of-the-art instrumentation and technology; (iv) provides a full cycle of treatment on the premises, employing - besides the best conventional therapies - protocols for novel targeted therapies and clinical trials for ‘precision medicine’.

Focus
Clinical and basic research makes the Institute of Candiolo a center of excellence focussed on the study, prevention, and treatment of the dreadful complication of cancer, metastasis.
Molecular diagnosis and “precision” medicine
The success of targeted therapies is based on the rationale that the target molecule is ‘druggable’ - as a consequence of the genetic anomaly - in the tumor but not in healthy tissues. Therefore the target molecule deactivation has consequences restricted to the neoplastic mass, with a minimum of ‘off-target’ consequences, leading to generic organ damage. This notion has two important clinical outcomes: first of all, before treating patients with a given targeted therapy, it is necessary to verify the presence of the genetic lesion “predictive” of sensitivity to the drug. Second - in the perspective of targeted therapies - tumors will be classified not only according to their site of origin and/or morphological features, but also by the molecular lesion(s) which earmark them and, at the same time, make them vulnerable to a targeted treatment. Therefore, new therapies are not only “targeted” but also “personalized”. This new approach is called “precision medicine”.

Clinical Research
At the Institute, oncologists, surgeons and radiotherapists cooperate with scientists to design clinical trials based on molecular data, intended to verify hypotheses and generate novel ones. In order to make this cooperation productive, the Institute manages a daily net of interactions involving formal aspects (seminars and meetings), training (refresher courses and lessons), and operational efforts (contacts with pharmaceutical companies, and management of regulatory instruments). Clinical Research is the last and more direct haven to improve the assistance to cancer patients, providing them with the most appropriate, novel, safe and effective therapeutic approach, in accordance with the genetic profile of their own tumor, as an ultimate means of increasing their life expectancy.

Investigational Clinical Oncology (INCO)
Cancer is a complex disease, tied to genetic lesions that increase in number over time, as a consequence of genetic instability and exposure to environmental carcinogens. Thus, a cell clone proliferates and invades the adjacent tissues without control. Cancer cells show several genetic anomalies that tend to increase as time passes. Cancer’s heterogeneity makes it a hard-to-attack desease because of its multiple and continuously changing target. The molecular lesions that cause and sustain most tumors are, however, finite in number (the bona fide oncogenes). These findings have driven clinical pharmacology to commit to an epochal effort to create drugs, called “targeted”, able to contrast the function of specific oncogenes. The strategy of the Institute at Candiolo intends to make significant contributions to the field of cancer targeted therapy by: (i) identifying pathologies and recruiting patients sensitive to the therapies currently in use; (ii) planning and performing - in international networks - the related clinical trials; (iii) developing translational and preclinical research aimed at designing new targeted therapies.

Translational Research (ECMO: Experimental Clinical Molecular Oncology)
Translational research is the “heart” of the Institute, bridging the gap between basic and clinical research. Based on recent technological advances, genomic analysis makes possible –in a significant percentage of cases– the identification of genetic alteration(s) with a “driver” role in tumor development. However, the contribution of each lesion to the transformed phenotype remains elusive. Moreover, there is still insufficient knowledge of the mechanisms that control the lack of response to targeted therapies, even in the presence of the molecular target (primary resistance), as well as of the mechanisms that lead to a progressive attenuation of the response after prolonged treatment (acquired resistance). ECMO research aims at the fulfillment of some ambitious Goals to integrate the traditional prognostic and diagnostic factors with a detailed characterization of the genetic and functional alterations of the tumor; to identify new malfunctioning regulatory pathways in cancer; to isolate and study cancer stem cells; to develop new preclinical platforms that can reliably disclose - and understand in detail– the prospective results of clinical practice. The generation of this kind of knowledge is necessary to design clinical trials that will no longer be based on empirical observations but on a strong rationale.

Basic Research
The current knowledge of the mechanisms of cancer onset and progression is provided by basic disciplines, such as genetics, cell and developmental biology. Thanks to these studies, it is possible to classify tumors not only according to the basis of their site of origin and histopathological features, but, notably, according to the identification of the genetic lesion(s) that support their growth. Basic Research tasks at the Institute are aimed at understanding the mechanisms that control normal cell functions responsible for proliferation, and at analyzing how these mechanisms are corrupted during neoplastic transformation. The topics include signal transduction, DNA duplication, cell division, differentiation, senescence, apoptosis and cell motility. Recent studies suggest that anti-neoplastic therapy is really effective not only when it hits the appropriate molecular target (vide infra), but especially when it hits the cells feeding the tumor mass. Indeed, most of the cells of the neoplastic mass are quite innocuous and can be attacked with classical therapies, while only a small fraction of them are resistant to treatment and able to regenerate the tumor. This small subpopulation includes the “cancer stem cells” – strictly related to normal “stem cells” – which control the development of our organism during embryonic life and allow us to renew worn parts in adult life. The up-to-date conceptualization of Cancer defines it as a “somatic, genetic disease of the stem cells”.
(rwf - V.10/16)

Scientific Direction- Staff

Phone: 011.993.3601
Email: antonella.cignetto@ircc.it

Contacts

Istituto di Candiolo
Strada Provinciale, 142 km 3,95
10060 Candiolo, Torino-Italy

CENTRALINO
011-9933.111

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