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Review
. 2020 Jan-Dec;27(1):1073274820983013.
doi: 10.1177/1073274820983013.

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

Alessandro Rizzo  1   2 , Alessandro Di Federico  1   2 , Angela Dalia Ricci  1   2 , Giorgio Frega  1   2 , Andrea Palloni  1   2 , Rachele Pagani  1   2 , Simona Tavolari  2   3 , Mariacristina Di Marco  1   2 , Giovanni Brandi  1   2
Affiliations
Review

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

Alessandro Rizzo et al. Cancer Control. 2020 Jan-Dec.

Abstract

Background: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA).

Methods & results: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials.

Conclusions: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.

Keywords: BRAF; biliary tract cancer; cholangiocarcinoma; dabrafenib; trametinib.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Schematic figure reporting anatomical subgroups of biliary tract cancer and commonly occurring gene aberrations; ampl: amplifications; BAP1: BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase); dCCA: distal cholangiocarcinoma; eCCA: extrahepatic cholangiocarcinoma; FGFR2: Fibroblast Growth Factor Receptor 2; GBC: gallbladder cancer; HER2: Human Epidermal growth factor Receptor 2; iCCA: intrahepatic cholangiocarcinoma; IDH: isocitrate dehydrogenase 1; mut: mutations; pCCA: perihilar cholangiocarcinoma; PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha.
Figure 2.
Figure 2.
Schematic representation of signaling pathways in biliary tract cancer, with a particular focus on the mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK), or RAS/RAF/MEK/ERK pathway, with BRAF and MEK inhibitors.
See this image and copyright information in PMC

References

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