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Molecular Markers and Targeted Therapy for Hepatobiliary Tumors: 2nd Edition

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 October 2026 | Viewed by 858

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Guest Editor
Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Hokkaido, Japan
Interests: photoimmunotherapy; endoscopy biliary tract cancer; pancreatic cancer; pancreatitis; acute pancreatitis model; mesenchymal stem cells
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Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue “Molecular Markers and Targeted Therapy for Hepatobiliary Tumors”, available at https://www.mdpi.com/journal/cancers/special_issues/4N88QYY1R8.

The poor prognoses of hepatobiliary malignancies such as cholangiocarcinoma and hepatocellular carcinoma, with 5-year relative survival rates of about 20%, are attributed to their difficult early detection and fewer curative, less-invasive anticancer therapies. Recently, some molecular markers have been reported, using new technologies such as liquid biopsy, organoids, exosome isolation, and single cell analysis. Based on these, several targeted therapies have also been reported in preclinical and clinical settings. Furthermore, appropriate molecular markers for assessing the efficacy of anti-cancer therapies are also required in order to maximize and manage therapies and improve prognosis.

This Special Issue aims to publish research related to cutting-edge/preclinical molecular markers for diagnosis or treatment assessment and targeted therapies for hepatobiliary malignancies. Consequently, the development of future research leading to improvements of clinical outcomes is anticipated.

We are pleased to invite you to submit articles on the above-mentioned topics. In this Special Issue, original research articles and reviews are welcome. Research areas include, but are not limited to, the following: molecular biology; pathology; genetics; organoids; exosome; chemotherapy; phototherapy.

I look forward to receiving your contributions.

Dr. Masaki Kuwatani
Guest Editor

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-anonymized 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
  • hepatocellular carcinoma
  • molecule
  • gene
  • chemotherapy
  • phototherapy

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Published Papers (1 paper)

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Research

15 pages, 1828 KB  
Article
High CD73 Expression Is Associated with Poor Prognosis in Biliary Tract Cancer Through Reduced Stromal Tumor-Infiltrating Lymphocytes
by Shoya Shiratori, Kazumichi Kawakubo, Kanako C. Hatanaka, Takuma Kobayashi, Teppei Konishi, Yoshiki Shinomiya, Soichiro Oda, Shunichiro Nozawa, Hiroki Yonemura, Ryo Sugiura, Kazuaki Harada, Yoshitsugu Nakanishi, Takehiro Noji, Shinya Tanaka, Satoshi Hirano, Masaki Kuwatani, Yutaka Hatanaka and Naoya Sakamoto
Cancers 2026, 18(6), 975; https://doi.org/10.3390/cancers18060975 - 18 Mar 2026
Cited by 1 | Viewed by 644
Abstract
Background: Biliary tract cancer (BTC) is an aggressive malignancy with limited therapeutic options and a poor prognosis. CD73 is upregulated under hypoxic conditions and promotes tumor progression. However, its clinical role in BTC and interaction with tumor-infiltrating lymphocytes (TILs) remain unclear. This study [...] Read more.
Background: Biliary tract cancer (BTC) is an aggressive malignancy with limited therapeutic options and a poor prognosis. CD73 is upregulated under hypoxic conditions and promotes tumor progression. However, its clinical role in BTC and interaction with tumor-infiltrating lymphocytes (TILs) remain unclear. This study aimed to elucidate the association between CD73 expression and prognosis in BTC, as well as its impact on the tumor microenvironment (TME) and TILs. Methods: This retrospective study included 100 patients who underwent curative BTC surgery at Hokkaido University Hospital between 2018 and 2023. Formalin-fixed tumor specimens were analyzed using DeepPathFinder™ (biomy Inc., Tokyo, Japan), an AI-based digital pathology platform enabling objective quantification of CD73 expression and lymphocyte infiltration within tumoral (T) and stromal (S) compartments. Immunohistochemistry for CD3, CD8, Foxp3, and CD163 was used to identify T-cell subsets and macrophages. Associations between CD73, TIL subsets, and overall survival (OS) were assessed using the Kaplan–Meier, Cox regression, and Spearman correlation analyses. Results: High T-CD73 expression was associated with shorter OS (hazard ratio [HR] = 1.97, p = 0.041), whereas S-CD73 showed no prognostic relevance. Conversely, high S-TIL density was correlated with improved survival (HR = 0.49, p = 0.032). T-CD73 expression was negatively correlated with stromal CD3+ and CD8+ T-cell densities, indicating selective suppression of stromal cytotoxic T-lymphocyte (CTL) infiltration. No significant correlations were observed between Foxp3+ T cells and CD163+ M2 macrophages. Conclusions: CD73 upregulation in tumor cells impairs stromal CTL and TIL activity, leading to a poor prognosis. Spatial distribution, rather than total TIL number, better reflects effective anti-tumor immunity. Full article
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