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Published on: August 7, 2020
Targeting tumor microenvironment for cholangiocarcinoma: Opportunities for precision medicine
Riccardo Carloni1, Alessandro Rizzo2, Angela Dalia Ricci3
1Department of Specialized, Experimental and Diagnostic Medicine, University of Bologna, Via Giuseppe Massarenti, 9, Bologna 40138, Italy; Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni, 15, Bologna 40138, Italy.
Abstract:
Systemic treatments (e.g., chemotherapy and targeted therapies) have limited efficacy for patients with locally advanced - unresectable - and metastatic cholangiocarcinoma (CCA), with an overall survival of less than a year. Tumor microenvironment (TME) represents the ecosystem surrounding the tumor which comprises immune cells, fibroblasts, endothelial cells, and a wide range of soluble factors. CCA TME is characterized by an abundant desmoplastic stroma, exhibits a high heterogeneity and it plays a central role in cancer onset and progression. There is growing evidence suggesting that it is possible to target TME in association with other treatment modalities, such as cytotoxic chemotherapy or targeted therapies, paving the way to possible combination strategies with a synergistic effect. Herein, we describe the components of CCA TME - such as cancer-associated fibroblasts and other cells of pivotal importance - with their most relevant interactions, focusing on the preclinical rationale for the development of effective anticancer treatments.
Insights
Targeting the cholangiocarcinoma tumor microenvironment (TME) offers new therapeutic strategies. Understanding TME components and interactions is key for developing effective combination treatments against this challenging cancer.
Area of Science:
- Oncology
- Cancer Biology
- Tumor Microenvironment Research
Background:
- Systemic treatments for advanced cholangiocarcinoma (CCA) show limited efficacy, with poor patient survival rates.
- The tumor microenvironment (TME) significantly influences CCA progression and presents a potential therapeutic target.
- CCA TME is characterized by a dense desmoplastic stroma and high cellular heterogeneity.
Purpose of the Study:
- To elucidate the components and interactions within the cholangiocarcinoma tumor microenvironment.
- To explore the preclinical rationale for targeting the TME in combination with existing therapies.
- To identify novel therapeutic strategies for locally advanced, unresectable, and metastatic CCA.
Main Methods:
- Review of current literature on cholangiocarcinoma TME composition.
- Analysis of cellular and molecular interactions within the CCA TME.
- Preclinical assessment of TME-targeting strategies.
Main Results:
- The CCA TME comprises diverse cells, including cancer-associated fibroblasts and immune cells, which critically impact tumor behavior.
- Specific interactions within the TME promote cancer progression and resistance to conventional therapies.
- Targeting TME components shows promise for synergistic effects when combined with chemotherapy or targeted agents.
Conclusions:
- The cholangiocarcinoma TME is a crucial determinant of treatment response and disease progression.
- Targeting the TME, particularly cancer-associated fibroblasts, represents a promising avenue for novel CCA therapies.
- Combination strategies involving TME modulation may overcome limitations of current systemic treatments for CCA.
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