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Review
. 2019 Mar 29:11:2623-2642.
doi: 10.2147/CMAR.S157092. eCollection 2019.

Biliary tract cancers: current knowledge, clinical candidates and future challenges

Noor-Ul-Ain Tariq  1   2 , Mairéad G McNamara  1   2 , Juan W Valle  1   2
Affiliations
Review

Biliary tract cancers: current knowledge, clinical candidates and future challenges

Noor-Ul-Ain Tariq et al. Cancer Manag Res. .

Abstract

Biliary tract cancers (BTCs) are rare with poor prognosis. Due to the advent of genomic sequencing, new data have emerged regarding the molecular makeup of this disease. To add to the complexity, various subtypes also harbor a varied genetic composition. The commonly mutated genes associated with this cancer are KRAS, EGFR, IDH, FGFR and BAP1. Various clinical studies are looking at targeting these genetic mutations. Another therapeutic area of note is the potential for the use of immunotherapy in patients with BTC. Although BTC may be a result of chronic inflammation, this does not necessarily translate into increased immunogenicity. This literature review discusses the diverse molecular and immune-related pathways in patients with BTC and their potential therapeutic implications.

Keywords: biliary tract cancer; extrahepatic cholangiocarci-noma; gallbladder cancer; genome sequencing; immunotherapy; intrahepatic cholangiocarcinoma; molecular targets.

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Conflict of interest statement

Disclosure Noor-ul-Ain Tariq received honoraria for lecturers, participation in writing guidelines and travel reimbursements in 2014 from Boehringer Ingelheim and received funding from the Timpson fellowship. Boehringer Ingelheim or Timpson have no influence over the contents of this review. Mairéad G McNamara was advisory board member of Ipsen, SHIRE, Celgene and Sirtex, received research support from NuCana BioMed Ltd. and SHIRE, received honoraria for participation in Speaker’s Bureau from Pfizer and Ipsen and received travel expenses from Bayer. Juan W Valle received travel grants from Celgene, Ipsen, Novartis, NuCana for more than 5 years, received honoraria for participation in Speakers’ Bureau for Abbott, Celgene, Ipsen, Novartis, Pfizer and Sir-tex and provided consulting or advisory role for for Abbott, Agios, AstraZeneca, Baxalta, Bioven, Celgene, Delcath, Genoscience Pharma, Incyte, Ipsen, Keocyt, Lilly, Merck, MidaTech, Mundipharma, Novartis, NuCana, PCI Biotech, Pfizer, Pieris Pharmaceuticals and QED Pharmaceuticals. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Anatomical sub-variants of BTC. Abbreviations: AVC, ampulla of Vater cancer; BTC, biliary tract cancer; EHC, extrahepatic cholangiocarcinoma; GBC, gallbladder cancer; IHC, intrahepatic cholangiocarcinoma.
Figure 2
Figure 2
Important signaling pathways of potential therapeutic significance in patients with BTC. Abbreviations: AKT/PKB, protein kinase B; ARID1A, AT-rich interactive domain containing protein 1A; BAP1, BRCA1-associated protein 1; BRAF, V-Raf murine sarcoma viral oncogene homolog B; BTC, biliary tract cancer; Dvl, disheveled protein; ErbB1, erythroblastic leukemia viral oncogene 1; ErbB2, erythroblastic leukemia viral oncogene 2; FGFR, fibroblast growth factor receptor; FZD, frizzled family; HDAC, histone deacetylase; IDH, isocitrate dehydrogenase; KRAS, Kirsten rat sarcoma viral oncogene homolog; MAPK/ERK pathway, mitogen-activated protein kinase/extracellular signal-regulated kinase pathway; mTOR, mammalian target of rapamycin; NADP, nicotinamide adenine dinucleotide phosphate; NADPH (reduced), nicotinamide adenine dinucleotide phosphate; PDGFR, plasma-derived growth factor receptor; PI3KCA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit A; PKA, protein kinase; PORC, serine O-palmitoyltransferase porcupine protein; PTEN, phosphatase and tensin homolog; RNF43, ubiquitin E3 ligase ring finger 43; TCF, T cell factor; VEGFR, vascular endothelial growth factor receptor; Wnt, Wingless-related integration; ZNRF3, E3 ubiquitin ligase zinc and ring finger 3.
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References

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