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Biliary tract cancers (BTCs), for their low incidence, have been often considered together. Gallbladder cancer (GBC) is the most common biliary tract malignancy, characterized by late diagnosis and poor prognosis, and although it is considered a rare tumor in western countries, other areas of the world show considerable incidence rates. In 2010, results from the large phase III ABC-02 clinical trial on GBC identified the gemcitabine and cisplatin combination as the most effective first-line regimen for both GBC and other BTCs. Since then, various systemic therapies have proven active in BTCs in both first- and second-line settings. Molecular profiling has highlighted important genetic differences between GBC and other BTCs, opening new ways for targeted therapy in advanced disease where standard chemotherapies show marginal benefit. Genome-wide data analysis have shown that GBC molecular landscape offer possible strategies for precision medicine approaches, and a better molecular understanding of the GBC is needed to better stratify patients for treatment. In this review, we discuss the molecular targetable agents for GBC, including the results that emerged by clinical trials exploring new treatment strategies.

Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options; in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.