Emerging pharmaceutical therapies for targeting cholangiocarcinoma microenvironment and chemokine pathways
ARMAND N. YAZDANI1, MICHAELA PLETSCH1, ABRAHAM CHORBAJIAN1, DAVID ZITSER1, VIKRANT RAI1,2,*
1 College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
2 Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA
* Corresponding Author: VIKRANT RAI. Email: 
BIOCELL https://doi.org/10.32604/biocell.2024.056252
Received 18 July 2024; Accepted 25 September 2024; Published online 14 October 2024
Abstract
Mixed cholangiocarcinoma is a rare and aggressive neoplastic proliferation of biliary tract epithelial cells, accounting for up to 20% of primary liver cancers. It is the second most common primary liver malignancy with a 5-year survivability of less than 10% at diagnosis and is associated with various inflammatory diseases. Current management involves systemic chemotherapy, targeted radiation, and surgical resection, but long-term survival remains low, especially for surgically unresectable cases. Novel discoveries and understandings of the tumor microenvironment reveal new opportunities for targeted therapies for cholangiocarcinoma. Specifically, new pharmaceuticals including cell-based vaccines, tumor-associated neutrophils, and hepatic stellate cells may make good therapeutic targets. Tumor-reactive stroma and cancer-associated fibroblasts are also heavily implicated in disease progression. This comprehensive review aims to discuss emerging pharmaceutical therapies for targeting the cholangiocarcinoma microenvironment and chemokine pathways involved in the pathogenesis of cholangiocarcinoma followed by a risk-benefit analysis of proposed pharmaceutical therapies for treatment. A literature search on PubMed, Google Scholar, and PMC was done including the terms cholangiocarcinoma, targeted therapies, chemokine pathways, microenvironment, therapeutic targets, chemotherapy, and immune cell, alone or in combination. The articles in the English language and published in the last 10–15 years were selected to discuss in this review article. Selective therapies targeting tumor microenvironment can be fruitful in inducing tumor apoptosis and suppressing cholangiocarcinoma proliferation. Immunosuppressive therapies and immune checkpoint inhibitors also demonstrate promise in improving patient outcomes, specifically in patient’s intolerance to chemotherapy.
Keywords
Cholangiocarcinoma; Chemokine pathways; Tumor microenvironment; Therapeutic targets
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