Gemcitabine plus cisplatin remains the standard first-line systemic therapy for advanced cholangiocarcinoma and offers a median survival of approximately 1 year. No standard regimens beyond the first line and no targeted or immunotherapy agents are approved yet in this disease. Development of molecular targeted therapy in this heterogenous and relatively rare malignancy continues to be a challenging area. The rapidly growing precision medicine efforts have uncovered the underlying mutational landscape of this lethal disease and paved the way for molecularly oriented clinical trials. The early results from such trials like those exploring IDH and FGFR2 derangements have highlighted its promising potential as alternative therapeutic options. Additionally, advances in cancer immunology have identified certain correlates as biomarkers of response to immune modulatory approaches. For instance, the presence of tumor DNA mismatch repair (MMR) deficiency and/or microsatellite instability (MSI), in 5% to 10% of cholangiocarcinoma, is associated with high rates and durability of responses to immune checkpoint blockade. Beside checkpoint inhibitors, other types of immune therapeutics like peptide and dendritic cell-based vaccines and adoptive cell therapies have been developed and are undergoing active evaluation in cholangiocarcinoma. With further research effort, the integration of tumor molecular profiling in trials exploring targeted immunotherapy will lead to better understanding of the predictive role of various molecular and immune biomarkers and ultimately shine the horizon for this patient population.
Keywords: Adoptive cell transfer; Bile duct cancer; Cancer vaccines; Checkpoint inhibitors; Targeted therapy.
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