Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, the inventors explored the role and the clinical relevance of circular RNA circLTBP2 in iCCA. In particular, CircLTBP2 (hsa_circ_0032603) was identified as a novel TGFβ-induced circRNA in several CCA cell lines. CircLTBP2 promotes tumor cell proliferation, migration and resistance to gemcitabine-induced apoptosis in vitro and tumor growth in vivo. Mechanistically, circLTBP2 acts as a competitive RNA regulating notably the activity of the tumor suppressor microRNA miR-338-3p, leading to the overexpression of its pro-metastatic targets. The restoration of miR-338-3p levels in iCCA cells reversed the pro-tumorigenic effects driven by circLTBP2, including the resistance to gemcitabine-induced apoptosis. In addition, circLTBP2 expression predicted a reduced survival, as detected in tumor tissues but also in serum exosomes isolated from patients with iCCA. In conclusion, CircLTBP2 is a novel effector of the pro-tumorigenic arm of TGFβ and a clinically relevant biomarker easily detected from liquid biopsies in iCCA. Thus, the present invention relates to the circulating RNA circLTBP2 as a biomarker and biotarget in intrahepatic cholangiocarcinomas.