Description
Study of the molecular, genetic and epigenetic mechanisms at the origin of the resistance of tumors to the main types of systemic treatment, such as molecular target therapy, anti-angiogenic therapy, immunotherapy. The research is conducted both at a pre-clinical level, using appropriate in vitro and murine tumor models, and by analyzing biological samples of patients treated with these drugs. It makes use of multi-omic and inter-disciplinary technological approaches.
Background
Experimental oncology has historically represented a fundamental incubator for the conception of current models of knowledge of tumor biology, summarized by the so-called “Hallmarks of cancer”, as well as the starting point for the development of innovative therapies for cancer that in the last decades have become available to a growing audience of cancer patients. Examples in this sense are provided by molecular targeting therapies for so-called operable genes, or by therapies that modulate the tumor microenvironment, such as anti-angiogenic therapy and immunotherapy, which collectively contribute to achieving precision oncology. One of the main challenges of this sector is currently that of translating this great wealth of knowledge into a measurable improvement of diagnostic and therapeutic perspectives for patients, combining observations that come from the pre-clinical world with others obtained directly from the clinic.
Rationale
Precision oncology is a booming area of medicine made possible by: (i) increasing availability of molecular targets in tumors and of drugs designed around these targets and (ii) by the concrete possibility of identifying the genetic alterations that can be activated in tumors in an increasing number of patients. However, the therapeutic success of this approach risks to be undermined by the phenomenon of tumor heterogeneity and resistance to systemic therapies, the mechanisms of which are still insufficiently understood. There are already numerous recent examples that indicate that both basic research, using suitable in vitro or animal models, and translational research, based on the analysis of biological samples from patients, can provide innovative ideas for the implementation of precision oncology. and overcoming the resistance to treatment.
The IRCCSs are generally well placed to contribute to these developments, both by virtue of their technological endowment and the human capital they have. However, it is important to aggregate this know-how around priority and homogeneous themes capable of promoting intra- and inter-IRCCS interactions, also through the promotion of dedicated research programs. An example of this at the IOV came from the recent approval of a research program on liquid biopsy in oncology. As part of this program, various advanced molecular methods have been integrated for mutational profiling and the search for therapeutic targets with relevant clinical questions in oncology, with the ultimate goal of producing results that, in addition to scientific value, also have clinical relevance and can be used to improve patient care.
Global Goals
- Implementation of liquid biopsy for the identification of operable genetic alterations and dynamic monitoring of the therapeutic response in conditions of particular clinical relevance.
- Development of advanced technological platforms for the preclinical study of the mechanisms of resistance to anti-tumor drugs.
- Development of innovative preclinical models for the study of new therapeutic combinations capable of overcoming drug resistance.
Expected and measurable results over the three-year period
- Number of patents filed on issues relating to precision oncology (e.g. predictive response markers or resistance markers) and increase in the related royalties received.
- At least 50% increase over the previous three years in the number of spontaneous translational oncology studies at the IOV as coordinator of multicenter studies.
- Validation of at least one innovative liquid biopsy approach demonstrating clinical utility in a selected group of neoplastic patients.
| Titolo | Testata | IF grezzo | Autori |
|---|---|---|---|
| Liquid Biopsy of Cerebrospinal Fluid Enables Selective Profiling of Glioma Molecular Subtypes at First Clinical Presentation | CLINICAL CANCER RESEARCH | 11,50 | Francesca Orzan, Francesca De Bacco, Lazzarini Elisabetta, Giovanni Crisafulli, Alessandra Gasparini, Angelo Dipasquale, Ludovic Barault, Marco Macagno, Pasquale Persico, Federico Pessina, Beatrice Bono, Laura Giordano, Pietro Zeppa, Antonio Melcarne, Paola Cassoni, Diego Garbossa, Armando Santoro, Paolo M. Comoglio, Indraccolo Stefano, Matteo Simonelli, Carla Boccaccio |
| Targeting NOTCH1 in combination with antimetabolite drugs prolongs life span in relapsed pediatric and adult T-acute lymphoblastic leukemia xenografts | EXPERIMENTAL HEMATOLOGY & ONCOLOGY | 11,40 | Sonia Minuzzo, Valentina Agnusdei, Marica Pinazza, Adriana A. Amaro, Sacchetto Valeria, Ulrich Pfeffer, Bertorelle Roberta, Orietta Spinelli, Valentina Serafin, Indraccolo Stefano |
| Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 11,30 | Boso Daniele, Martina Tognon, Curtarello Matteo, Sonia Minuzzo, Ilaria Piga, Valentina Brillo, Lazzarini Elisabetta, Jessica Carlet, Ludovica Marra, Chiara Trento, Andrea Rasola, Ionica Masgras, Leonardo Caporali, Fabio Del Ben, Giulia Brisotto, Matteo Turetta, Roberta Pastorelli, Laura Brunelli, Filippo Navaglia, Esposito Giovanni, Grassi Angela, Indraccolo Stefano |
| High-and intermediate-risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium | JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY | 9,20 | C. Pellegrini, L. Cardelli, P. Ghiorzo, L. Pastorino, M. Potrony, Z. García-Casado, Lisa Elefanti, I. Stefanaki, M. Mastrangelo, S. Necozione, P. Aguilera, A. Rodríguez-Hernández, L. Di Nardo, T. Rocco, L. Del Regno, C. Badenas, C. Carrera, J. Malvehy, C. Requena, J. Bañuls, A.J. Stratigos, K. Peris, Menin Chiara, D. Calista, E. Nagore, S. Puig, M.T. Landi, M.C. Fargnoli |
| Long-term proliferation of immature hypoxia-dependent JMML cells supported by a 3D in vitro system | BLOOD ADVANCES | 7,60 | Alice Cani, Caterina Tretti Parenzan, Chiara Frasson, Elena Rampazzo, Pamela Scarparo, Samuela Francescato, Federico Caicci, Vito Barbieri, Rosato Antonio, Simone Cesaro, Marco Zecca, Concetta Micalizzi, Laura Sainati, Martina Pigazzi, Alessandra Biffi, Barbara Buldini, Franco Locatelli, Luca Persano, Riccardo Masetti, Geertruij Te Kronnie, Silvia Bresolin |
| Repurposing Verapamil to Enhance Killing of T-ALL Cells by the mTOR Inhibitor Everolimus | ANTIOXIDANTS | 7,00 | Silic-Benussi Micol, Sharova Evgeniya, Corradin Alberto, Loredana Urso, Vittoria Raimondi, Cavallari Ilaria, Barbara Buldini, Samuela Francescato, Sonia A. Minuzzo, D’Agostino Donna Mia, Ciminale Vincenzo |
| Ataxia-Telangiectasia Mutated Loss of Heterozygosity in Melanoma | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 5,60 | Lorenza Pastorino, Bruna Dalmasso, Eleonora Allavena, Irene Vanni, Filippo Ugolini, Gianna Baroni, Michela Croce, Antonio Guadagno, Francesco Cabiddu, Virginia Andreotti, William Bruno, Gabriele Zoppoli, Lorenzo Ferrando, Enrica Teresa Tanda, Francesco Spagnolo, Menin Chiara, Rosaria Gangemi, Daniela Massi, Paola Ghiorzo |
| Exosome-Based Liquid Biopsy Approaches in Bone and Soft Tissue Sarcomas: Review of the Literature, Prospectives, and Hopes for Clinical Application | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 5,60 | Chiara Agnoletto, Ymera Pignochino, Chiara Caruso, Cecilia Garofalo |
| Molecular Modeling Unveils the Effective Interaction of B-RAF Inhibitors with Rare B-RAF Insertion Variants | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 5,60 | Scaini Maria Chiara, Piccin Luisa, Davide Bassani, Scapinello Antonio, Pellegrini Stefania, Poggiana Cristina, Catoni Cristina, Tonello Debora, Pigozzo Jacopo, Dall’Olmo Luigi, Rosato Antonio, Stefano Moro, Vanna Chiarion Sileni, Menin Chiara |
| Biodistribution of Intratracheal, Intranasal, and Intravenous Injections of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles in a Mouse Model for Drug Delivery Studies | PHARMACEUTICS | 5,40 | Anna Maria Tolomeo, Zuccolotto Gaia, Ricardo Malvicini, Giada De Lazzari, Alessandro Penna, Chiara Franco, Federico Caicci, Fabio Magarotto, Santina Quarta, Michela Pozzobon, Rosato Antonio, Maurizio Muraca, Federica Collino |
| Antitumor Activity of the Xanthonoside XGAc in Triple-Negative Breast, Ovarian and Pancreatic Cancer by Inhibiting DNA Repair | CANCERS | 5,20 | Juliana Calheiros, Liliana Raimundo, João Morais, Ana Catarina Matos, Sonia Anna Minuzzo, Indraccolo Stefano, Emilia Sousa, Marta Correia Da Silva, Lucília Saraiva |
| Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2 | CANCERS | 5,20 | Francesco Sessa, Rossella Nicoletti, Cosimo De Nunzio, Porreca Angelo, Stefano Maria Magrini, Vincenzo Mirone, Andrea Tubaro, Sergio Serni, Paolo Gontero, Marianna Noale, Stefania Maggi, Mauro Gacci |
| p53/TP53 Status Assessment in Gastroesophageal Adenocarcinoma | CANCERS | 5,20 | Boldrin Elisa, Piano Maria Assunta, Francesco Bernaudo, Rita Alfieri, Biasin Maria Raffaella, Montagner Isabella Monia, Volpato Alice, Mattara Genny, Francesco Lamacchia, Magni Giovanna, Rosato Antonio, Scapinello Antonio, Pilati Pierluigi, Curtarello Matteo |
| Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach | CANCERS | 5,20 | Aamir Amin, Morello Marzia, Maria Raffaella Petrara, Rizzo Beatrice, Francesco Argenton, De Rossi Anita, Giunco Silvia |
| TERT promoter mutations in head and neck squamous cell carcinoma: A systematic review and meta-analysis on prevalence and prognostic significance | ORAL ONCOLOGY | 4,80 | Paolo Boscolo-Rizzo, Giancarlo Tirelli, Jerry Polesel, Egidio Sia, Veronica Phillips, Daniele Borsetto, De Rossi Anita, Giunco Silvia |
| Titolo | Testata | IF grezzo | Autori |
|---|---|---|---|
| Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg? | BRITISH JOURNAL OF CANCER | 9,08 | Bonanno Laura, Dal Maso, Alessandro, Alberto Pavan, Zulato Elisabetta, Lorenzo Calvetti, Pasello Giulia, Guarneri Valentina, Conte Pierfranco, INDRACCOLO STEFANO |
| Longitudinal liquid biopsy anticipates hyperprogression and early death in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors | BRITISH JOURNAL OF CANCER | 9,08 | Zulato Elisabetta, Del Bianco Paola, Nardo Giorgia, Ilaria Attili, Alberto Pavan, Andrea Boscolo Bragadin, Ludovica Marra, Pasello Giulia, FASSAN MATTEO, Fiorella Calabrese, Guarneri Valentina, Conte Pierfranco, INDRACCOLO STEFANO, Bonanno Laura |
| E2F1 copy number variations in germline and breast cancer: a retrospective study of 222 Italian women | MOLECULAR MEDICINE | 6,38 | Maria Santa Rocca, Clara Benna, Cosci Ilaria, Alberto Marchet, Carlo Foresta |
| Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients | Frontiers in Oncology | 5,74 | Maria Raffaella Petrara, Sarah Shalaby, Elena Ruffoni, Martina Taborelli, Carmona Francesco, Giunco Silvia, Del Bianco Paola, Pierluca Piselli, Diego Serraino, Umberto Cillo, Riccardo Dolcetti, Patrizia Burra, DE ROSSI ANITA |
| Liquid Biopsies in Cancer Diagnosis, Monitoring and Prognosis | Biomedicines | 4,76 | Paola Ulivi, INDRACCOLO STEFANO |
| EGFR T790M testing through repeated liquid biopsy over time: a real-world multicentric retrospective experience | Journal of Thoracic Disease | 3,01 | ALESSANDRO DAL MASO, Del Bianco Paola, Francesco Cortiula, Nardo Giorgia, Zulato Elisabetta, Bonanno Laura, Alessandro Follador, Giovanna De Maglio, Pasello Giulia, INDRACCOLO STEFANO |