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Cancers
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Immunotherapy and Targeted Agents for Biliary Tract Cancer
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Immunotherapy and Targeted Agents for Biliary Tract Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 22698

Special Issue Editors

Prof. Dr. Massimo Aglietta

E-Mail Website
Guest Editor
Department of Medical Oncology, Candiolo Cancer Institute, FPO—IRCCS—Str. Prov.le 142, km 3.95, 10060 Candiolo (TO), Italy
Interests: Sarcoma; gastrointestinal cancers; early clinical trials
Dr. Giovanni Brandi

E-Mail Website
Guest Editor
1. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Giuseppe Massarenti 9, Bologna, Italy
2. Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy
Interests: immunotherapies; pancreaticobiliary cancers; microbiota; immunogenic cell death; rare sarcomas; epithelial tumors

Special Issue Information

Dear Colleagues,

Biliary tract cancer (BTC) is the second most common primary liver tumor accounting for approximately 10-15% of all hepatobiliary malignancies and 3% of all gastrointestinal neoplasms. BTCs include a heterogeneous group of malignancies usually divided into intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of Vater cancer, according to anatomical location. Although traditionally considered rare tumors in Western countries, their incidence and mortality rate are on the whole rising worldwide. In particular, the incidence of intrahepatic cholangiocarcinoma is expected to further increase in the near future.

Currently, radical surgery with microscopically negative resection margins is the only potentially curative therapy available, although most patients are diagnosed in late disease stages (locally advanced/unresectable or metastatic). Moreover, even after complete surgical resection, the recurrence rate is high and the 5-year overall survival rate remains discouraging (20-35% at 5 years). As a result of the increasing availability of genomic sequencing data, many signaling pathways and new genetic aberrations involved in the carcinogenesis of BTC have recently been delineated and IDH1 mutations and FGFR2 fusions have been positioned as the two main driver alterations in intrahepatic cholangiocarcinoma and are being actively explored with specific antitargeted agents. However, many other alterations as NTRK rearrangements or BRAF mutations are also emerging as new potential targets in BTC. On the other hand, the role of immunotherapy in BTC is currently under investigation and checkpoint inhibitors are still looking for their niche in BTC. In this Special Issue, experts in this field will review the current immunotherapeutic and targeted approaches to the management of patients with the spectrum of BTC.

Prof. Dr. Massimo Aglietta
Prof. 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. 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

  • biliary tract cancer
  • cholangiocarcinoma
  • targeted therapy
  • immunotherapy
  • checkpoint inhibitors

Published Papers (4 papers)

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Review

18 pages, 708 KiB  
Review
Immunotherapy in Advanced Biliary Tract Cancers
by Alice Boilève, Marc Hilmi, Cristina Smolenschi, Michel Ducreux, Antoine Hollebecque and David Malka
Cancers 2021, 13(7), 1569; https://doi.org/10.3390/cancers13071569 - 29 Mar 2021
Cited by 17 | Viewed by 5151
Abstract
Biliary tract cancers are rare tumors with a poor prognosis. Two-thirds of these primary liver malignancies are diagnosed at advanced stages where therapeutic options are limited. Whereas several molecular targeted therapies emerge in biliary tract cancers, immunotherapy is still investigational, the only approved [...] Read more.
Biliary tract cancers are rare tumors with a poor prognosis. Two-thirds of these primary liver malignancies are diagnosed at advanced stages where therapeutic options are limited. Whereas several molecular targeted therapies emerge in biliary tract cancers, immunotherapy is still investigational, the only approved immunotherapy to date being the immune checkpoint inhibitor pembrolizumab for the small fraction of patients with microsatellite-instable tumors. In microsatellite-stable, pre-treated biliary tract cancers, single-agent immune checkpoint blockade has a limited albeit often long-lasting clinical activity in a still ill-defined subgroup of patients. The identification of predictive biomarkers will allow a better selection of patients that may benefit from immunotherapy. Combinations of immunotherapies with each other, with chemotherapy or targeted molecular therapies are being investigated in early lines of therapy, including first-line. Full article
(This article belongs to the Special Issue Immunotherapy and Targeted Agents for Biliary Tract Cancer)
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11 pages, 808 KiB  
Review
IDH Signalling Pathway in Cholangiocarcinoma: From Biological Rationale to Therapeutic Targeting
by Massimiliano Salati, Francesco Caputo, Cinzia Baldessari, Barbara Galassi, Francesco Grossi, Massimo Dominici and Michele Ghidini
Cancers 2020, 12(11), 3310; https://doi.org/10.3390/cancers12113310 - 09 Nov 2020
Cited by 25 | Viewed by 4433
Abstract
Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of [...] Read more.
Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of biliary tract cancers from an “orphan” to a “target-rich” disease. Recently, mutations in isocitrate dehydrogenase genes (IDH1/2) and fusions of the fibroblast growth factor receptor have emerged as the most amenable to molecularly targeted inhibition, with several compounds actively investigated in advanced-phase clinical trials. Specifically, the IDH1 inhibitor ivosidenib has been the first targeted agent to show a survival benefit in a randomized phase III trial of cholangiocarcinoma patients harboring IDH1 mutations. In this review article, we will focus on the IDH1/IDH2 pathway, discussing the preclinical rationale of its targeting as well as the promises and challenges of the clinical development of IDH inhibitors in biliary tract cancers. Full article
(This article belongs to the Special Issue Immunotherapy and Targeted Agents for Biliary Tract Cancer)
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15 pages, 1034 KiB  
Review
Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures
by Alessandro Rizzo, Simona Tavolari, Angela Dalia Ricci, Giorgio Frega, Andrea Palloni, Valeria Relli, Massimiliano Salati, Elisabetta Fenocchio, Annamaria Massa, Massimo Aglietta and Giovanni Brandi
Cancers 2020, 12(11), 3256; https://doi.org/10.3390/cancers12113256 - 04 Nov 2020
Cited by 8 | Viewed by 3125
Abstract
Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when [...] Read more.
Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions. Full article
(This article belongs to the Special Issue Immunotherapy and Targeted Agents for Biliary Tract Cancer)
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31 pages, 1324 KiB  
Review
Evolution of the Experimental Models of Cholangiocarcinoma
by Annamaria Massa, Chiara Varamo, Francesca Vita, Simona Tavolari, Caterina Peraldo-Neia, Giovanni Brandi, Alessandro Rizzo, Giuliana Cavalloni and Massimo Aglietta
Cancers 2020, 12(8), 2308; https://doi.org/10.3390/cancers12082308 - 17 Aug 2020
Cited by 75 | Viewed by 9175
Abstract
Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA [...] Read more.
Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA molecular pathogenesis, highlighting its extreme heterogeneity and high frequency of genetic and molecular aberrations. Effective preclinical models, therefore, should be based on a comparable level of complexity. In the past years, there has been a consistent increase in the number of available CCA models. The exploitation of even more complex CCA models is rising. Examples are the use of CRISPR/Cas9 or stabilized organoids for in vitro studies, as well as patient-derived xenografts or transgenic mouse models for in vivo applications. Here, we examine the available preclinical CCA models exploited to investigate: (i) carcinogenesis processes from initiation to progression; and (ii) tools for personalized therapy and innovative therapeutic approaches, including chemotherapy and immune/targeted therapies. For each model, we describe the potential applications, highlighting both its advantages and limits. Full article
(This article belongs to the Special Issue Immunotherapy and Targeted Agents for Biliary Tract Cancer)
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