Novel precision therapies for cholangiocarcinoma: an overview of clinical trials

Usón, Pedro Luiz Serrano; Bearss, Jeremiah J.; Babiker, Hani M.; Borad, Mitesh J.

doi:10.1080/13543784.2023.2173064

Cited by 1 publication

(1 citation statement)

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“…Importantly, clinical trial studies reveal that two kinds of MTA, the FGFR tyrosine kinase inhibitor and the IDH1 inhibitor, were reported to be effective in treating advanced chemotherapy-resistant CCAs after progression on first-line systemic therapy with FGFR2 fusions/rearrangements and IDH1 mutations, respectively [ 7 , 8 , 9 , 10 ]. In addition, HER2 and BRAF inhibitors are undergoing incorporation into the conventional systemic chemotherapy [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Inflamed Tumor Microenvironment and Methylation/Downregulation of Antigen-Presenting Machineries in Cholangiocarcinoma

Nishida

Aoki

Morita

et al. 2023

Cancers

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Cholangiocarcinoma (CCA) is a refractory cancer; a majority of CCAs represents a non-inflamed tumor phenotype that should be resistant to treatment, including immune checkpoint inhibitors (ICIs). In this study, we aimed to understand the molecular characteristics associated with non-inflamed CCAs. The genetic/epigenetic status of 36 CCAs was obtained from the Cancer Genome Atlas (PanCancerAtlas). CCAs were classified based on immune class using hierarchical clustering analysis of gene expressions related to tumor-infiltrating lymphocytes. The associations between immune class and genetic/epigenetic events were analyzed. We found that the tumors with alterations in FGFR2 and IDH1/2 had a “non-inflamed” tumor phenotype. A significant association was observed between the non-inflamed group and the downregulation of genes involved in antigen presentation (p = 0.0015). The expression of antigen-presenting machineries was inversely correlated with their DNA methylation levels, where 33.3% of tumors had an upregulation/low-methylation pattern, and 66.7% of tumors had a downregulation/high-methylation pattern. All tumors in the “inflamed” group exhibited an upregulation/low-methylation pattern. In contrast, 24 of 30 tumors in the non-inflamed group represent the downregulation/high-methylation pattern (p = 0.0005). Methylation with downregulation of antigen-presenting machineries is associated with the “non-inflamed” tumor phenotype of CCAs. This evidence provides important insights for developing new strategies for treating CCA.

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