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The Molecular Biology of Cholangiocarcinoma
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The Molecular Biology of Cholangiocarcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 818

Special Issue Editors

Prof. Dr. Kevin Gaston

E-Mail Website
Guest Editor
Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
Interests: cancer biology; transcription; gene regulation
Prof. Dr. Padma-Sheela Jayaraman

E-Mail Website
Guest Editor
Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
Interests: cancer biology; epigenetics; gene regulation

Special Issue Information

Dear Colleagues,

Our understanding of the molecular biology of cancer of the bile duct, or cholangiocarcinoma (CCA), has advanced rapidly over the last 10-15 years. Molecular profiling has identified mutations that are prevalent in different CCA sub-types, including IDH1/2 mutations and FGFR2 rearrangements, and these allow some patients to receive targeted treatment. Analysis of the CCA tumour microenvironment (TME) has also been transformed by the application of new approaches including multiplex spatial analysis of gene and protein expression and single-cell sequencing. However, important issues remain, such as the lack of proven routes to early detection, the lack of freely accessible large-scale data sets, and patchy, or non-existent, patient access to molecular profiling.

We welcome primary research papers and reviews that focus on the cell and the molecular biology underlying these areas and related topics in cholangiocarcinoma research, and that thereby help to identify and close gaps in our knowledge of this disease.

Prof. Dr. Kevin Gaston
Prof. Dr. Padma-Sheela Jayaraman
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • cholangiocarcinoma
  • biliary tract cancer
  • early detection
  • targeted therapy
  • tumour microenvironment
  • spatial biology
  • genomics
  • transcriptomics
  • proteomics

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Published Papers (1 paper)

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Review

38 pages, 7326 KB  
Review
Spectrum of Biliary and Nonbiliary Neoplasms Growing and Spreading Within the Lumen of the Bile Ducts
by Yasuni Nakanuma, Yasunori Sato, Yuko Kakuda and Takuma Oishi
Cancers 2026, 18(9), 1356; https://doi.org/10.3390/cancers18091356 - 24 Apr 2026
Viewed by 451
Abstract
In the hepatobiliary system, the majority of neoplasms grow within the hepatic parenchyma; however, some arise, grow, and/or spread within the lumen of the intrahepatic large bile ducts and the perihilar/distal bile ducts (collectively referred to as large bile ducts), representing specialized ductal [...] Read more.
In the hepatobiliary system, the majority of neoplasms grow within the hepatic parenchyma; however, some arise, grow, and/or spread within the lumen of the intrahepatic large bile ducts and the perihilar/distal bile ducts (collectively referred to as large bile ducts), representing specialized ductal organs associated with unique peribiliary glands and being distinct from the intrahepatic small bile ducts and bile ductules embedded within the hepatic parenchyma. Precursors of cholangiocarcinoma (CCA) arising within the lumen of large bile ducts have recently been proposed. Neoplasms growing and spreading within the lumen of large bile ducts have been categorized into four groups and are discussed here in light of updated pathological findings. (i) Precursor(s) of CCA arising in the large bile ducts (large-duct-type intrahepatic CCA and perihilar/distal CCA): These precursors include high-grade biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal oncocytic papillary neoplasm (IOPN). High-grade BilIN presents as a flat, microscopic lesion with dysplastic cytoarchitectural alterations and grows along the luminal surface of large bile ducts, whereas the latter two present as grossly visible polypoid or tumorous lesions composed of papillary, villous, or tubular proliferation of neoplastic epithelium with delicate fibrovascular cores. These lesions may eventually progress to invasive CCA. Intraductal tubulopapillary neoplasm of the bile duct (ITPN), previously categorized as another precursor of CCA arising in large bile ducts, appears to represent a heterogeneous group of neoplasms with respect to progression and presumed cell of origin. Some ITPNs are frequently associated with nodular invasive carcinoma resembling small-duct-type intrahepatic CCA (SD-iCCA) and share genetic alterations with SD-iCCA; such cases may arise in association with small bile ducts or bile ductules. In contrast, other ITPNs exhibit cystic changes with tubulopapillary features and may arise in association with peribiliary glands or cysts. (ii) Secondary growth and spread of biliary neoplasms: This category comprises several patterns. First, intraepithelial neoplastic spread directly and continuously from the primary neoplastic lesion is observed in almost all cases of high-grade BilIN, IPNB, and IOPN; it spreads laterally along the luminal surface of the proximal and distal bile ducts and extends vertically into the adjacent peribiliary glands. Intraluminal cast-like spread in the bile ducts adjacent to the primary neoplastic lesion also occurs in some precursor lesions, particularly in ITPN. Implantation of a biliary neoplasm from one part of the biliary tract to another results in discontinuous, multifocal biliary neoplasms, particularly in IPNB, and occurs mainly in the distal bile ducts relative to the main tumor. Multicentric tumorigenesis may contribute to the multifocal development of precursors and CCA in the bile ducts. The accumulation of additional genetic alterations, beyond the common mutations detected in primary tumors, may contribute to metachronous recurrence of CCA after curative resection of the primary biliary tumor. Cancerization of the duct (COD) by CCA may also contribute to secondary growth and spread within the bile duct lumen. Specifically, flat-type cancerization of pre-existing non-neoplastic bile ducts, resembling high-grade BilIN, occurs in approximately one-third of hilar CCA cases. Intraductal polypoid, cast-like cancerization within the lumen of adjacent bile ducts, resembling polypoid precursors of CCA, can also occur in approximately one-tenth of SD-iCCA. (iii) Prominent intraductal polypoid growth of invasive CCA: Invasive CCA rarely presents with predominant intraductal polypoid carcinoma that is continuous with periductal infiltrating CCA; this pattern can be referred to as polypoid invasive CCA. (iv) Nonbiliary neoplasms presenting bile duct tumor thrombus (BDTT): BDTT associated with hepatocellular carcinoma and with extrahepatic malignancies extending into the bile duct lumen can mimic the intraluminal growth and spread patterns of the above-mentioned biliary neoplasms. In conclusion, intraluminally growing biliary neoplasms in the large bile ducts comprise a heterogeneous group that can be reasonably classified into four categories. This categorization may facilitate understanding of these intrabiliary growing neoplasms. Full article
(This article belongs to the Special Issue The Molecular Biology of Cholangiocarcinoma)
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