Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

• Published in: Cancers Vol. 12; no. 8; p. 2039
• Main Authors: Chakrabarti, Sakti, Kamgar, Mandana, Mahipal, Amit
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-07-2020; MDPI
• Subjects: Apoptosis; Biliary tract; Chemotherapy; Clinical trials; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Epidermal growth factor; FDA approval; Fibroblast growth factor receptors; Fibroblasts; Growth factors; Hepatitis; Isocitrate dehydrogenase; Ligands; Medical prognosis; Mutation; Next-generation sequencing; Pathophysiology; Review; Studies; Surgery; Tumors; United States > US; biliary tract cancer; targeted therapy; gallbladder cancer; next-generation sequencing; pemigatinib; ivosidenib; circulating tumor DNA (ctDNA); cholangiocarcinoma; molecular profiling
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12082039

Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and
mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. In this review, we provide a contemporaneous appraisal of the evolving targeted therapies and the ongoing clinical trials that will likely transform the therapeutic paradigm of BTC.