PTEN: An Individual Therapy Target Of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is a relatively rare, but increasing more common, hepatobiliary cancer. ICC, the second most common liver cancer, is an aggressive cancer typically diagnosed at an advanced stage with poor prognosis. By now we know little about the origin and molecular mechanisms of this cancer, and several molecular-targeted therapies have been assessed in clinical trials. However, there is no standard therapy for ICC, and additional therapeutic drugs are needed urgently.The phosphatase and tensin homologue(PTEN) was identified by two independent groups to be frequently disrupted in multiple sporadic tumour types and targeted by germline mutations in patients with cancer predis-position syndromes such as Cowden disease. It was the most vital tumor suppressor since P53. The importance of the physiological function of PTEN is illustrated by its frequent disruption in cancer. By suppressing the phosphoinositide3-kinase(PI3K) –AKT –mammalian target of rapamycin(mTOR) pathway through its lipid phosphatase activity, PTEN governs a plethora of cellular processes including survival, proliferation, energy metabolism and cellular architectur.In our study, PTEN expression and function are frequently limited in some ICC tumor samples. When sequencing PTEN cDNA in ICC tumor, we found mutation existing in some cases. Moreover, it really surprise us that PTEN loss and PTEN wild type ICC cells have contrary destiny when restored PTEN protein. PTEN Loss will die while PTEN WT can resist this treatment. With the help of Patient-Derived Xenografts mouse model, we get the same results in vivo. Thus, PTEN can be a therapy target of ICC patients for personalized medicine development.