Ricerc@Sapienza

Intrahepatic cholangiocarcinoma (iCCA) is malignant tumor arising from the bile duct and peribiliary glands of the liver. This cancer is aggressive and with a very poor prognosis: about 50% of patients with untreated disease die within 4 months of presentation. The only curative treatment option is surgery, unfortunately limited to early stage disease. Thus, the early detection of iCCA is crucial to counteract the disease. To date, the diagnosis of iCCA requires multidisciplinary approaches and is still a challenge because of its paucicellular nature, anatomic location, and silent clinical character. Therefore, there is a need for accurate and sensitive circulating markers to distinguish the iCCA in respect to other liver malignancies and to increase the chance of having curative treatment interventions.
iCCA is characterized by a peculiar, dense and reactive desmoplastic stroma that provides the anatomical supporting structure for tumor mass and promotes tumor progression. The iCCA stromal microenvironment is mainly represented by an altered and excessive accumulation of extracellular matrix (ECM) components that arises from the fibrogenic activity of cancer-associated myofibroblasts (CAFs). Particularly, the iCCA-associated desmoplastic reaction requires a dynamic ECM remodeling with continuous degradation and new synthesis and secretion of ECM components by CAFs. Thus, ECM leakage proteins released into the circulation may reflect the state of the iCCA onset and progression and may be the most likely candidates as reliable, specific and non-invasive biomarkers. Supported by preliminary proteomic data showing many iCCA-specific ECM proteins released in the liquid tumor microenvironment, the present proposal aims to develop a panel of circulating biomarkers for the early and accurate tumor detection.