Abstract
Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease.
Highlights
Cholangiocarcinoma (CCA), first identified by Steiner and Higginson [1] belongs to a heterogeneous group of malignancies that occur at any point of the biliary tree [2]
A reduction in extracellular glutamine concentration has been demonstrated in most malignancies and it seems to have a role on the cell susceptibility to different apoptosis triggers
Iron is necessary for cellular replication and growth, so it is an essential element for life
Summary
Cholangiocarcinoma (CCA), first identified by Steiner and Higginson [1] belongs to a heterogeneous group of malignancies that occur at any point of the biliary tree [2]. CCA is mainly diagnosed in an advanced clinical stage of the disease, when curative treatment is generally unsuccessful [20] This is in part due to the lack of clinical manifestation of the tumor in the early stage, especially in case of iCCA, and in part to the absence of specific and sensitive biomarkers. To reduce global mortality from cholangiocarcinoma, efforts must be multifaceted and focus on prevention, early identification of high-risk individuals and prompt diagnosis as well as molecular based targeted therapies for established disease [14]. In this scenario, the concept of tumor metabolism is worth particular interest for several reasons:. Due to the high heterogeneity in the metabolic pathways that occur in different tumors, and even inside the same tumour [26], this review will highlight the main metabolic processes that occur in CCA progression
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