Molecular Pathogenesis of Cholangiocarcinoma

Abstract

Epidemiological data from the last years show an increasing trend of incidence and mortality of cholangiocarcinoma (CC) worldwide. Many pathophysiologic aspects of this neoplasia are still unknown and need to be fully discovered. However, several progresses were recently made in order to establish the molecular mechanisms involved in the transformation and growth of malignant cholangiocytes. The principal concept that at least seems to be established is that cholangiocarcinogenesis is a multistep cellular process evolving from a normal condition of the epithelial biliary cells through a chronic inflammation status ending with malignant transformation. The bad prognosis related to CC justifies why a better identification of the molecular mechanisms involved in the growth and progression of this cancer is required for the development of effective preventive measures and valid treatment regimens. This Paper describes the scientific progresses made in the last years in defining the molecular pathways implicated in the generation of this devastating disease.

Expression of COX-2 and VEGF-C in cholangiocarcinomas at different clinical and pathological stages

“…In recent years, many studies have shown that COX-2 is overexpressed in bladder, non-small cell lung, and gastric cancers (Grammas, 2011;Fukuhara et al, 2013;Rosas et al, 2014;Thomas, 2014). Additional studies showed that COX-2 expression was closely associated with local angiogenesis, tumor cell infiltration, proliferation, and apoptosis (Grammas, 2011;Fava and Lorenzini, 2012;Fukuhara et al, 2013;Rosas et al, 2014). VEGF is the most important factor in angiogenesis and has been widely investigated.…”

“…Its prognosis is generally poorer than other malignancies such as gastric cancer and colorectal cancer (Fava and Lorenzini, 2012;Aishima et al, 2013;Marino et al, 2013). Thus, it is important to identify new treatments for cholangiocarcinoma.…”

Cholangiocarcinoma: from molecular biology to treatment

“…Interleukin-6 (IL-6) seems like a critical signaling molecule in the pathogenesis of various cancers and can be found upstream or downstream of several other oncogenes [17][18][19][20][21]. In this context, the CC is no exception, and IL-6 is a key cytokine in the pathogenesis of this neoplasm being its proliferative effect confirmed ( Fig.…”

Profil moléculaire des tumeurs hépatobiliaires: vers de nouvelles pistes, facteurs prédictifs et cibles thérapeutiques

“…Le mauvais pronostic de ces tumeurs s'explique par le diagnostic tardif qui est souvent fait à un stade avancé de la maladie, inopérable ou métastatique, et par l'absence de traitement standardisé efficace. Ces dernières années, les recherches se sont donc appliquées à décrire les mécanismes molécu-laires de la carcinogenèse des CVB afin d'identifier de nouvelles pistes pour d'éventuelles thérapies ciblées [9]. La capacité à identifier les différents sous-types moléculai-res sera cruciale pour progresser dans la prise en charge des CVB.…”