Cholangiocarcinoma: molecular pathways and therapeutic opportunities.

[cholangiocarcinoma]

Cholangiocarcinoma (CCA ) is an aggressive biliary tract malignancy with limited treatment options and low survival rates . Currently , there are no curative medical therapies for CCA . Recent advances have enhanced our understanding of the genetic basis of this disease , and elucidated therapeutically relevant targets . Therapeutic efforts in development are directed at several key pathways due to genetic aberrations including receptor tyrosine kinase pathways , mutant IDH enzymes , the PI 3 K -AKT-mTOR pathway , and chromatin remodeling networks . A highly desmoplastic , hypovascular stroma is characteristic of CCAs and recent work has highlighted the importance of targeting this pathway via stromal myofibroblast depletion . Future efforts should concentrate on combination therapies with action against the cancer cell and the surrounding tumor stroma . As the mutational landscape of CCA is being illuminated , molecular profiling of patient tumors will enable identification of specific mutations and the opportunity to offer directed , personalized treatment options .