Dr. Matteo Curtarello, Biologist, PhD
Matteo Curtarello is a Biologist. He graduated with honors in Medical Biotechnology in 2004 and in Cellular and Molecular Biology in 2010 at the University of Bologna. He obtained his PhD Degree in Virology and Microbial Biotechnology in 2008 at the University of Padova.
Since 2009, Matteo Curtarello has focused his research activity mainly on the metabolic effects of anti-angiogenic therapy in preclinical models of epithelial ovarian cancer (EOC). He demonstrated that poorly glycolytic xenografts regressed following protracted anti-VEGF therapy, whereas highly glycolytic tumors became rapidly resistant. Moreover, protracted anti-VEGF therapy selects for highly glycolytic cells and this metabolic switch is stable and precedes tumor relapse. Overall, his results suggest that the highly glycolytic phenotype modulates therapeutic response to anti-angiogenic therapy and could be involved in treatment resistance (Cancer Res., 2015). During this time, he has improved his technical and scientific skills, also thanks to the collaboration with several national/international research groups.
He keeps on investigating the effects of anti-VEGF therapy, focusing his attention on modulation of lipid metabolism (Cells, 2019) and evolution of intra-tumor metabolic heterogeneity, in collaboration with Dr. Stefano Indraccolo (IOV).
Furthermore, he has recently switched to clinical translational research with particular interest to the discovery of prognostic and predictive biomarkers in cancer (Int J Mol Sci., 2020). His research activity, in tight collaboration with Surgical Oncology Unit and Pathology Unit (IOV), is aimed to evaluate the application of liquid biopsy to improve clinical management of patients with gastric-esophageal oncologic disease.
Advanced translational research (RTA) Laboratory
Immunology and Molecular Oncology Unit
Department of Translational Oncology and Health Services
Research activity
Liquid biopsy (cell free DNA, cfDNA) approach to track tumor response to therapy and/or relapse in gastric esophageal oncologic diseases (GEODs)
New diagnostic strategies with predictive/prognostic potential could help to better characterize GEODs. The combined use of cfDNA and high sensitivity molecular assays will allow a more accurate monitoring of patients with the advantage of mini-invasiveness.
Research topic
Our research is focused on the validation in liquid biopsy of predictive/prognostic biomarkers that could improve clinical outcome of GEODs patients.
Background
GEODs include: 1) Gastric AdenoCarcinomas (GACs) and Esophageal AdenoCarcinomas (EACs) collectively termed GEAs; 2) Esophageal Squamous Cell Carcinomas (ESCCs); 3) dysplastic and metaplastic Barrett’s esophagus (BE).
Most EACs arise from BE through metaplasia – low-grade dysplasia (LGD) – high-grade dysplasia (HGD) axis. This observation has led to the development of endoscopic surveillance protocols for the identification of patients at risk for neoplastic progression. However, this approach is highly controversial because of inherent difficulties in the accurate identification of dysplastic lesions. On the contrary, ESCCs do not develop from a pre-neoplastic lesion and are molecularly different from EACs.
Recent advances in GEAs molecular characterization have led to the application of new therapeutic strategies that have increased patients survival. However, therapies response remains unpredictable due to inter-individual variability and lack of easily detectable prognostic/predictive indicators. Moreover, GEA is characterized by a high intra-tumor heterogeneity that is responsible for the partial failure of target therapies. Since diagnostic typing is currently based on immunohistochemistry (IHC) analysis of few biopsies, heterogeneity within the primary tumor cannot be detected, compromising the clinical response by an unsuitable therapeutic choice.
Thus, there is a need to find new tools for a more accurate GEODs classification that could guide subtype specific treatments. Moreover, it is very important to develop new strategies for a more efficient monitoring of cancer progression starting from pre-neoplastic lesions (especially for BE-LGD-HGD-EAC axis) and for a more suitable tracking of tumor response to therapy and/or relapse.
Recent studies have shown that cfDNA, released in the bloodstream by cancer cells, harbors genetic abnormalities specific of the primary tumor. Therefore, cfDNA could be a promising tool to better characterize GEODs and to improve clinical patients’ management.
Reasearch achievements
We demonstrated that in BE, EADC and ESCC it is possible to detect genetic and epigenetic alterations in cfDNA. Liquid biopsy evaluation could be therefore a useful no-invasive analysis for monitoring disease status. We aim to study the possibility to detect and follow molecular markers in cfDNA of GEA patients using high sensitive molecular techniques (PCR multiplex, digital-droplet PCR) suitable for both FFPE- and cfDNA samples. Currently, we are evaluating the concordance between molecular analysis and IHC diagnostic typing, focusing on the most important biomarkers in GEA patient’s management (HER2, p53, MSI).
Conclusions and perspectives
We demonstrated that in BE, EADC and ESCC it is possible to detect genetic and epigenetic alterations in cfDNA. Liquid biopsy evaluation could be therefore a useful no-invasive analysis for monitoring disease status. We aim to study the possibility to detect and follow molecular markers in cfDNA of GEA patients using high sensitive molecular techniques (PCR multiplex, digital-droplet PCR) suitable for both FFPE- and cfDNA samples. Currently, we are evaluating the concordance between molecular analysis and IHC diagnostic typing, focusing on the most important biomarkers in GEA patient’s management (HER2, p53, MSI).
Team members
Permanent staff
- Elisa Boldrin, PhD, Biologist
- Maria Assunta Piano, PhD, Biologist
Selected references
- Boldrin E, Curtarello M, Dallan M, Alfieri R, Realdon S, Fassan M, Saggior D. Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients. Int J Mol Sci. 2020 Feb 24;21(4):1547.
- Curtarello M, Tognon M, Venturoli C, Silic-Benussi M, Grassi A, Verza M,Minuzzo S, Pinazza M, Brillo V, Tosi G, Ferrazza R, Guella G, Iorio E, Godfroid A, Sounni NE, Amadori A, Indraccolo S. Rewiring of Lipid Metabolism and Storage in Ovarian Cancer Cells after Anti- VEGF Therapy. Cells. 2019 Dec 9;8(12):1601.
- Curtarello M, Zulato E, Nardo G, Valtorta S, Guzzo G, Rossi E, Esposito G, Msaki A, Pastò A, Rasola A, Persano L, Ciccarese F, Bertorelle R, Todde S, Plebani M, Schroer H, Walenta S, Mueller-Klieser W, Amadori A, Moresco RM, Indraccolo S. VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells. Cancer Res. 2015 Jan 1;75(1):120-33.