The prognosis of
cholangiocarcinoma remains poor in spite of the advances in
immunotherapy and molecular profiling, which has led to the identification of several targetable genetic alterations.
Surgical procedures, including both liver resection and
liver transplantation, still represent the treatment with the best curative potential, though the outcomes are significantly compromised by the early development of
lymph node metastases. Progression of
lymphatic metastasis from the primary
tumor to
tumor-draining lymph nodes is mediated by
tumor-associated lymphangiogenesis, a topic largely overlooked until recently. Recent findings highlight
tumor-associated lymphangiogenesis as paradigmatic of the role played by the tumor microenvironment in sustaining
cholangiocarcinoma invasiveness and progression. This study reviews the current knowledge about the intercellular signaling and molecular mechanism of
tumor-associated lymphangiogenesis in
cholangiocarcinoma in the hope of identifying novel therapeutic targets to halt a process that often limits the success of the few available treatments.