Options in Targeted Therapy for Advanced Cholangiocarcinoma: A 2024 Update

Abstract

Bile duct carcinomas have a different prognosis and genetic profile depending on their location; intrahepatic/extrahepatic or at the level of the gallbladder. Although in recent years there have been important advances in first-line therapy, second-line therapy in cholangiocarcinoma does not currently have a standard. Therefore at this level, there is an acute need for personalized treatment. The present article is a narrative review that aims to list the newest targeted therapeutic options for this type of cancer, based on identified genetic alterations. The literature selected for analysis includes phase 2 or 3 studies with targeted therapy in this disease and original articles no older than three years that describe the prevalence of the most common gene alterations in this type of cancer. PubMed/Medline, Scopus, and Clarivate-Web of Science databases were searched and keywords such as "cholangiocarcinoma," "biliary cancer," "targeted therapy," "gene amplifications," and "mutations" were used. This narrative review was designed taking into account the SANRA (Scale for the Assessment of Narrative Review Articles) criteria. The conclusions lead to the fact that next-generation sequencing testing is of particular usefulness in cholangiocarcinoma. Bile duct cancers are rich in targetable genetic alterations, and their treatment is in constant change, although much of the current data comes from phase II studies. There is a great need for the current options to be analyzed in phase III studies. Hence, the need of the oncological community to stay informed about targeted treatment options for cholangiocarcinoma is supported by the present article.

Keywords: cancer; gastroenterology; genetics; medicine; oncology.

Figure 1. The FGF pathway in brief.

After FGF (fibroblast growth factor) binds to the transmembrane receptor, FGFR (fibroblast growth factor receptor) dimerizes and activates the intracellular pathways. Through the JAK/STAT (Janus kinase/signal transduction and transcription activation), RAS (rat sarcoma virus)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated extracellular signal-regulated kinase) and PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B)/ERK pathways (extracellular signal-related kinase), DNA transcription is activated and consequently cell proliferation, migration, angiogenesis, and DNA repair take place. Picture generated at BioRender.com.