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Francesco Prof. Novelli


Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death in the Western world. The majority of cases are diagnosed in the advanced stages, making curative therapy impossible and leading to poor prognosis and incidence equalling mortality. Untreated metastatic pancreatic cancer has a median survival of 3-5 months and 6-10 months for locally advanced disease, making the overall 5-year survival less than 5%. At present efficacious and specific biomarkers for the early detection of PDAC are lacking in the clinical practice, for this reason the 80% of PDAC cases are inoperable at the time of diagnosis. Approximately 90% of patients with pancreatic cancer receive a diagnosis of advanced loco-regional disease, the treatment is palliative and, with current treatments, the median overall survival ranges only from 9 to 10 months. Management options range from systemic chemotherapy alone to combined forms of treatment with chemoradiation therapy and chemotherapy. For these reasons is important to set up new vaccination protocols and new immunotherapeutic strategies to beat this aggressive tumor.
From 2002, our group is involved in the development of new strategies for the diagnosis and the immunotherapy of PDAC. In particular, we used SERological Proteome Analysis (SERPA) to identify a panel of molecules that are recognized by PDAC patients’ sera antibodies (Figure 1).

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Figure 1. By using SERological Proteome Analysis (SERPA), we test the ability of PDAC patients’ sera to recognize “proteomic maps” (proteome) of pancreatic cancer cell lines. These maps derives from a Two-Dimensional Electrophoresis (2-DE) separation of protein extracts; each protein is represented on the map by a unique spot characterized by a specific isoelectric point and molecular weight. Moreover, by Two-Dimensional Electrophoresis Western Blot (2-DE WB), we identified some spots (proteins) that are recognized by PDAC patients’ sera and we further evaluated these spots by Mass Spectrometry (MS). 
Some of these molecules, such as alpha-Enolase, are phosphorylated during PDAC carcinogenesis and are able to induce the production of antibodies useful to diagnose PDAC. To confirm the presence of these biomarkers also at early stages of PDAC, we used Genetically Engineered Mice (GEM) able to develop spontaneously PDAC. With this murine model, we can identify new molecules useful for the early diagnosis and for the treatment (e.g. alpha-enolase DNA vaccination) of PDAC. 



1) Identify biomarkers for early diagnosis of pancreatic cancer.
2) Develop immunotherapeutic and vaccination strategies for the treatment of pancreatic cancer. 


Proteomics, autoantibodies, tumor associated antigens, pancreatic cancer, vaccination, immunotherapy, genetically engineered mice, anti-tumor immunity 


 

 

 

 

Last update: 21/09/2018 23:32
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