Therapeutic Strategies in Cholangiocarcinoma

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gastrointestinal Oncology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 13384

Special Issue Editor

Hôpital Beaujon, Clichy, France
Interests: colorectal pathology; intrahepatic cholangiocarcinomas

Special Issue Information

Dear Colleagues,

Cholangiocarcinomas (CCA) are heterogeneous highly malignant tumor developed from the biliary tract. It is the second most common primary liver malignancy. Its incidence in Europe and North America has significantly increased without any reason clearly identified. The prognosis is dismal mainly due to tumor aggressiveness, late diagnosis and poor response to current therapies. Three principal forms are described according to their location: intrahepatic, peri-hilar and distal CCA. Interestingly, each subtype has a distinct epidemiology, biology, prognosis, carcinogenesis and molecular alterations responsible of a specific clinical strategy management and with the importance to make an accurate diagnosis. The offer of therapeutic possibility in CCA is wide, ranging from surgery only potentially curative treatment for earlier stage of CCA to targeted therapies depending on molecular alterations. In this special issue about therapeutic strategies of CCA, we will discuss firstly, the importance of the diagnostic process from the point of view of the clinician, the pathologist and the radiologist. In a second step we will deal with the various current therapeutic possibilities. Finally, we will say a word on therapeutic perspectives.

Dr. Nathalie S. Guedj
Guest Editor

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Keywords

  • cholangiocarcinoma
  • therapeutic
  • diagnosis

Published Papers (5 papers)

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Review

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12 pages, 671 KiB  
Review
Cancer-Associated Fibroblasts and Extracellular Matrix: Therapeutical Strategies for Modulating the Cholangiocarcinoma Microenvironment
by Mirko Minini and Laura Fouassier
Curr. Oncol. 2023, 30(4), 4185-4196; https://doi.org/10.3390/curroncol30040319 - 14 Apr 2023
Cited by 2 | Viewed by 2365
Abstract
During the last decade, immunotherapy has radically changed perspectives on anti-tumor treatments. However, solid tumor treatment by immunotherapy has not met expectations. Indeed, poor clinical response to treatment has highlighted the need to understand and avoid immunotherapy resistance. Cholangiocarcinoma (CCA) is the second [...] Read more.
During the last decade, immunotherapy has radically changed perspectives on anti-tumor treatments. However, solid tumor treatment by immunotherapy has not met expectations. Indeed, poor clinical response to treatment has highlighted the need to understand and avoid immunotherapy resistance. Cholangiocarcinoma (CCA) is the second cause of hepatic cancer-related deaths because of drug inefficacy and chemo-resistance in a majority of patients. Thus, intense research is ongoing to better understand the mechanisms involved in the chemo-resistance processes. The tumor microenvironment (TME) may be involved in tumor therapy resistance by limiting drug access. Indeed, cells such as cancer-associated fibroblasts (CAFs) alter TME by producing in excess an aberrant extracellular matrix (ECM). Interestingly, CAFs are the dominant stromal component in CCA that secrete large amounts of stiff ECM. Stiff ECM could contribute to immune exclusion by limiting anti-tumor T-cells drop-in. Herein, we summarize features, functions, and interactions among CAFs, tumor-associated ECM, and immune cells in TME. Moreover, we discuss the strategies targeting CAFs and the remodeling of the ECM to improve immunotherapy and drug therapies. Full article
(This article belongs to the Special Issue Therapeutic Strategies in Cholangiocarcinoma)
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12 pages, 2224 KiB  
Review
Current Perspectives in Liver Transplantation for Perihilar Cholangiocarcinoma
by Francesco Giovinazzo, Marco Maria Pascale, Francesca Cardella, Matteo Picarelli, Serena Molica, Francesca Zotta, Annamaria Martullo, George Clarke, Francesco Frongillo, Antonio Grieco and Salvatore Agnes
Curr. Oncol. 2023, 30(3), 2942-2953; https://doi.org/10.3390/curroncol30030225 - 01 Mar 2023
Cited by 1 | Viewed by 2373
Abstract
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are [...] Read more.
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are considered unresectable at the time of diagnosis or exploration. When resective surgery is deemed unfeasible, liver transplantation (LT) could be an effective alternative. The overall survival rates after LT at 1 and 3 years are 91% and 81%, respectively. The overall five-year survival rate after transplantation is 73% (79% for patients with underlying PSC and 63% for de novo pCCA). Multicenter case series reported a 5-year disease-free survival rate of ~65%. However, different protocols, including neoadjuvant therapy, have been proposed. The scarcity of organ availability represents a crucial limiting factor in recommending LT preferentially in treating pCCA. Living donor transplantations and marginal cadaveric allografts have proven to be exciting options to overcome organ shortage. Management of jaundice and cholangitis is still challenging for these patients and could impact LT listing. Whether to adopt surgical resection or LT as standard-of-care in pCCA is still a matter of debate, and more prospective studies are needed. Full article
(This article belongs to the Special Issue Therapeutic Strategies in Cholangiocarcinoma)
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11 pages, 3181 KiB  
Review
Pathology of Cholangiocarcinomas
by Nathalie Guedj
Curr. Oncol. 2023, 30(1), 370-380; https://doi.org/10.3390/curroncol30010030 - 26 Dec 2022
Cited by 7 | Viewed by 2116
Abstract
Cholangiocarcinomas (CCA) are heterogeneous tumors that arise from epithelial cells of the biliary tract. They represent the second primary liver malignancy, after hepatocellular carcinoma. Recent epidemiological data show an increased incidence of intrahepatic CCA without any identified causes. According to their location on [...] Read more.
Cholangiocarcinomas (CCA) are heterogeneous tumors that arise from epithelial cells of the biliary tract. They represent the second primary liver malignancy, after hepatocellular carcinoma. Recent epidemiological data show an increased incidence of intrahepatic CCA without any identified causes. According to their location on the biliary tract, intrahepatic, perihilar (p) and distal (d) CCA can be individualized. Intrahepatic CCA (iCCA) are subdivided into small duct type iCCA and large duct type iCCA, according to the level or size of the biliary duct affected. These two subgroups are characterized by distinct risk factors, gross aspect, histopathological and molecular features, and therapeutic management. The role of biopsy in iCCA is to confirm the diagnosis and to eliminate various differential diagnostics, in particular, metastases. In p/d CCA, biopsy requires more invasive approaches, and tissue samples are difficult to obtain, leading to a high rate of false negatives. In this review, we will discuss the different classifications of CCA (anatomical and macroscopic). We will describe the various microscopic and phenotypic subtypes of CCA. Finally, we will deal with their mode of extension, the role of biopsy and pre-neoplastic lesions. Full article
(This article belongs to the Special Issue Therapeutic Strategies in Cholangiocarcinoma)
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14 pages, 324 KiB  
Review
Surgical Treatment of Distal Cholangiocarcinoma
by Leva Gorji and Eliza W. Beal
Curr. Oncol. 2022, 29(9), 6674-6687; https://doi.org/10.3390/curroncol29090524 - 17 Sep 2022
Cited by 6 | Viewed by 2911
Abstract
Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract and has a poor prognosis. dCCA is often clinically silent and patients commonly present with locally advanced and/or distant disease. For patients identified with early stage, [...] Read more.
Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract and has a poor prognosis. dCCA is often clinically silent and patients commonly present with locally advanced and/or distant disease. For patients identified with early stage, resectable disease, surgical resection with negative margins remains the only curative treatment strategy available. However, despite appropriate treatment and diligent surveillance, risk of recurrence remains high with nearly 50% of patients experiencing recurrence at 5 years subsequent to surgical resection; therefore, it is prudent to continue to optimize neoadjuvant and adjuvant therapies in order to reduce the risk of recurrence and improve overall survival. In this review, we discuss the clinical presentation, workup and surgical treatment of dCCA. Full article
(This article belongs to the Special Issue Therapeutic Strategies in Cholangiocarcinoma)

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7 pages, 586 KiB  
Perspective
Pemigatinib in Intrahepatic Cholangiocarcinoma: A Work in Progress
by Gennaro Gadaleta-Caldarola, Alessandro Rizzo, Vincenzo Dadduzio, Lucia Lombardi, Arianna Gadaleta-Caldarola, Stefania Infusino, Antonio Cusmai, Claudia Citrigno and Gennaro Palmiotti
Curr. Oncol. 2022, 29(10), 7925-7931; https://doi.org/10.3390/curroncol29100626 - 19 Oct 2022
Cited by 2 | Viewed by 2451
Abstract
Cholangiocarcinoma (CCA) is the second most frequent primary liver cancer, following hepatocellular carcinoma (HCC). Progress in the molecular understanding of CCA has led to the development of several agents, including FGFR inhibitors, such as pemigatinib, whose approval has marked a new era in [...] Read more.
Cholangiocarcinoma (CCA) is the second most frequent primary liver cancer, following hepatocellular carcinoma (HCC). Progress in the molecular understanding of CCA has led to the development of several agents, including FGFR inhibitors, such as pemigatinib, whose approval has marked a new era in this hepatobiliary malignancy. However, a number of questions remain unanswered, including the development of secondary resistance and the role of combination therapies, including FGFR inhibitors. Herein, we specifically focus on the current challenges and future research directions of pemigatinib use in CCA patients. Full article
(This article belongs to the Special Issue Therapeutic Strategies in Cholangiocarcinoma)
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