Dr. Matteo Curtarello, Biologist, PhD

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).