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Advanced Research on Cholangiocarcinoma: From Bench to Bedside
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Advanced Research on Cholangiocarcinoma: From Bench to Bedside

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 November 2025 | Viewed by 979

Special Issue Editors

Dr. Masaru Katoh

E-Mail Website1 Website2
Guest Editor
1. National Cancer Center, Tokyo, Japan
2. M & M Precision Medicine, Tokyo, Japan
Interests: precision medicine; FGF receptors; WNT signaling; epithelial–mesenchymal plasticity; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Tavolari

E-Mail Website
Guest Editor
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Interests: biliary tract cancer; molecular characterization; prognostic and predictive factors; cancer resistance; circulating and tissular biomarkers; experimental CCA models
Dr. Giovanni Brandi

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Interests: hepato-biliary-pancreatic cancers; risk factors; chemotherapy; targeted therapies; cancer treatment; precision medicine; microbiota
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cholangiocarcimanas (CCAs) are aggressive cancers arising along the biliary tree and classified according to their anatomical origin as intrahepatic (iCCA) or extrahepatic (eCCA), the latter encompassing perihilar and distal CCAs. The prognosis of CCAs in patients remains dismal as they are usually diagnosed at late stages of the disease when surgical resection is not possible and chemotherapy is mostly palliative. CCAs are notoriously difficult-to-treat cancers. Notwithstanding, the clinical development of targeted therapies, such as fibroblast growth factor receptor (FGFR) inhibitors and immune checkpoint inhibitors (ICIs), in combination with cytotoxic chemotherapy, is yielding promising results in selected patients with CCA.

In this Special Issue, original articles, case reports, review articles and commentaries addressing recent progress in CCA research, particularly regarding the following topics, are encouraged:

  1. Emerging etiologies and risk factors of CCAs;
  2. The whole-exome, whole-genome and RNA sequencing of CCA tumors;
  3. Single-cell or spatial biology analyses of CCAs;
  4. Patient-derived xenografts (PDXs) and patient-derived organdies (PDOs) as CCA models;
  5. Experimental in vivo models of CCAs;
  6. Gene panel tests of pre- and post-treatment patients with CCA;
  7. FGFR inhibitors for the treatment of patients with CCA;
  8. ICIs and combination therapy for patients with CCA;
  9. The development of novel therapeutics for patients with CCA;
  10. Predictive and prognostic tissular/circulating biomarkers in patients with CCA.

We look forward to receiving your submissions. Please note that all submissions must include data at the molecular level.

Sincerely,

Dr. Masaru Katoh
Dr. Simona Tavolari
Dr. Giovanni Brandi
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 short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • risk factors
  • next-generation sequencing
  • actionable targets
  • FGFR2
  • BAP1
  • IDH1
  • tissular/circulating biomarkers
  • cancer resistance
  • immune microenvironment
  • in vitro and in vivo models
  • clinical trials

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Published Papers (2 papers)

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12 pages, 1936 KiB  
Article
Mutant p53 Associates with Human Equilibrative Nucleoside 1 Upregulation and Better Response to Adjuvant Gemcitabine in Intrahepatic Cholangiocarcinoma Patients
by Marzia Deserti, Valeria Relli, Andrea Palloni, Francesco Vasuri, Deborah Malvi, Alessio Degiovanni, Simone Rimedio, Chiara Delbaldo, Chiara Deiana, Giovanni Brandi and Simona Tavolari
Int. J. Mol. Sci. 2025, 26(11), 5259; https://doi.org/10.3390/ijms26115259 - 30 May 2025
Viewed by 390
Abstract
The prognostic and predictive role of the human equilibrative nucleoside transporter 1 (hENT-1) has emerged in different cancer types, including intrahepatic cholangiocarcinoma (iCCA), but the mechanisms regulating its expression are poorly understood. Here, we investigated the link between p53 status and hENT-1 regulation [...] Read more.
The prognostic and predictive role of the human equilibrative nucleoside transporter 1 (hENT-1) has emerged in different cancer types, including intrahepatic cholangiocarcinoma (iCCA), but the mechanisms regulating its expression are poorly understood. Here, we investigated the link between p53 status and hENT-1 regulation in 38 iCCA patients and cell line models; the predictive role of p53 status in response to adjuvant gemcitabine was also investigated. A positive association between mutant p53 cells and hENT-1 expression was observed in iCCA tissue samples; furthermore, patients receiving adjuvant gemcitabine and expressing mutant p53 cells > 4% in tumor tissue had a longer disease-free survival (DFS) than patients expressing mutant p53 cells ≤ 4% (median 18.5 vs. 6 months, p = 0.0229). In iCCA cell line models, transient knockdown of mutant p53 resulted in a decrease in hENT-1 mRNA and protein expression; similarly, restoration of wild-type p53 function induced a significant reduction in hENT-1 mRNA and protein expression. Overall, these findings support a role of p53 status in the regulation of hENT-1 expression, suggesting an opposite effect (activating versus repressive) of mutant and wild-type p53 protein. Furthermore, although the present study should be considered as preliminary, our findings suggest a predictive role of p53 status in iCCA patients treated with gemcitabine, thus deserving future investigations in additional cohorts of cancer patients. Full article
(This article belongs to the Special Issue Advanced Research on Cholangiocarcinoma: From Bench to Bedside)
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6 pages, 1719 KiB  
Case Report
First Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma with Tasurgratinib Following Regulatory Approval: A Case Report from Clinical Practice
by Yuta Maruki, Chigusa Morizane, Mao Okada, Shota Harai, Yoshikuni Nagashio, Susumu Hijioka, Hideki Ueno and Takuji Okusaka
Int. J. Mol. Sci. 2025, 26(12), 5586; https://doi.org/10.3390/ijms26125586 - 11 Jun 2025
Viewed by 340
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with limited treatment options in advanced stages. Recently, targeted therapies against fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a promising approach for selected patients. Tasurgratinib, a selective FGFR1–3 inhibitor, was approved in [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with limited treatment options in advanced stages. Recently, targeted therapies against fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a promising approach for selected patients. Tasurgratinib, a selective FGFR1–3 inhibitor, was approved in Japan in 2024 for second-line treatment of FGFR2 fusion-positive biliary tract cancer. We report the case of a 55-year-old female with advanced iCCA harboring an FGFR2-BICC1 fusion, who experienced a rapid clinical response to tasurgratinib following disease progression on gemcitabine, cisplatin, and durvalumab (GCD). Following the failure of GCD therapy, treatment with oral tasurgratinib was initiated at 140 mg/day and subsequently reduced to 105 mg/day due to Grade 2 diarrhea. Within weeks, imaging and tumor markers indicated a partial response, accompanied by a reduction in ascites, and improved performance status. The response sustained for several months without evidence of disease progression. Notably, no substantial clinical hyperphosphatemia or anorexia was observed during treatment. This is the first report to describe the real-world clinical efficacy of tasurgratinib in an iCCA patient with FGFR2-BICC1 fusion. Our findings suggest that tasurgratinib can provide a rapid and durable response with manageable toxicity in molecularly selected patients who have progressed on standard therapies. Full article
(This article belongs to the Special Issue Advanced Research on Cholangiocarcinoma: From Bench to Bedside)
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