Immunotherapy and Targeted Therapy for Advanced Biliary Tract Cancer: Adding New Flavors to the Pizza

SIMPLE SUMMARY: Biliary tract cancers (BTCs) are a rare pathology. In the era of precision oncology, the development of next-generation sequencing (NGS) allowed a better understanding of molecular differences between each tumor. Alterations in genes such as the FGFR, HER2, IDH1, and BRAF, result in cancer development, growth, and proliferation. Recent drug development allowed for the use of medications that can target these alterations and inhibit cancer progression. Additionally, the understanding of how the immune system interacts with cancer cells also resulted in the use of immunotherapy in this difficult scenario, although we still do not know how to select the patients with a higher chance of response. Here, we review the most recent data regarding targeted treatment and immunotherapy in the scenario of BTC treatment, discussing not only the role that these medications have in modern oncology, but also the future perspectives for this challenging disease. ABSTRACT: Biliary tract cancers (BTCs) are a rare pathology and can be divided into four major subgroups: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and gallbladder cancer. In the era of precision oncology, the development of next-generation sequencing (NGS) allowed a better understanding of molecular differences between these subgroups. Thus, the development of drugs that can target these alterations and inhibit the abnormal pathway activation has changed the prognosis of BTC patients. Additionally, the development of immune checkpoint inhibitors and a better understanding of tumor immunogenicity led to the development of clinical trials with immunotherapy for this scenario. The development of biomarkers that can predict how the immune system acts against the tumor cells, and which patients benefit from this activation, are urgently needed. Here, we review the most recent data regarding targeted treatment and immunotherapy in the scenario of BTC treatment, while also discussing the future perspectives for this challenging disease.