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    Home > Active Ingredient News > Digestive System Information > Sci Transl Med: Significant progress! Wang Hongyang's team reveals new strategies for precision treatment of bile tube cancer.

    Sci Transl Med: Significant progress! Wang Hongyang's team reveals new strategies for precision treatment of bile tube cancer.

    • Last Update: 2020-10-04
    • Source: Internet
    • Author: User
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    The malignant degree of bile duodenal cancer is high, the progress is fast, the clinical treatment is mostly late, and many have relapsed metastasis, the surgical rate is low, the efficacy of conventional chemotherapy on bile duodenal cancer is very limited, in other tumors has shown clear efficacy of targeted treatment, immunotherapy and other means in bile duodenal cancer attempts are rarely successful examples.
    Hongyang, a member of the National Hepatology and Cancer Science Center of oriental hepato-biliary surgery hospital, has been working to solve this challenging clinical science problem.
    September 23, 2020, Science Translational Medicine, a sub-issue of the American journal Science, published a heavy-weight paper entitled "PTEN status decisions the chemosensitivity toproteasome resedion in cholangiocarcinoma" by a team of academicians.
    paper reveals that nearly 40% of bile tube cell carcinomas have the absence of the important anti-cancer gene PTEN, which makes protease activity significantly increased, directly affecting the malignant behavior of tumor cells.
    Through a series of screening and clinical studies have found that the use of multiple myeloma treatment drug Bortzomib can significantly inhibit the growth of these bile tube cancer cells;
    The work found that the anti-cancer gene PTEN regulates protease activity, clarifies its signal transducting pathway, and puts forward a new strategy for accurate target diagnosis and treatment of bile tube cancer, which is of great clinical significance and a fine example of translational medicine research.
    In short, the work found the anti-cancer gene PTEN on the protease activity regulation, clear its signal transductive pathway, and accordingly put forward a new strategy of precise target diagnosis and treatment of bile tube cancer, which has important clinical significance, but also a fine example of translational medicine research.
    cancer (cholangiocarcinoma) is a tumor with a very high degree of malignancy, which occurs in the capillary bile tube to the bile tube.
    can be divided into endo-hepatic bile tube cell carcinoma, liver door bile tube cancer and far-end bile tube cancer, but all originated from bile tube cortectal cells.
    bile tube cell carcinoma is the second largest malignant tumor after liver cell carcinoma, and its incidence has increased significantly in the past 40 years.
    the incidence of bile duodenal cell carcinoma hidden, found to be late, can cure the surgery rate is low, and the recurrence metastasis rate is very high.
    , the diagnosis and treatment of bile cell carcinoma in the last 10 years has not seen a significant breakthrough, the patient's post-treatment prognosis is poor, the five-year survival rate is less than 5%.
    Wang Hongyang academician task force first applied targeted depth sequencing screening to the presence of a variety of invigorating mutations of the anti-cancer gene PTEN in the liver bile tube cell carcinoma, the proportion of mutation cases is close to 40%;
    combined with molecular biology experimental analysis of the downstream signaling path, showed a significant increase in the activity of the downstream protease after the PTEN inactive mutation.
    the use of protease inhibitor Bortzomib to reverse the malignant ideotype of tumor cells with PTEN infestion mutations.
    team found that PTEN-missing cells had higher protein synthesis rates and higher protease activity than PTEN wild cells, and when protease inhibitors were applied, a large number of proteins aggregated and tumor cells died due to protein toxicity stress.
    team further discovered the existence of the PTEN-PI3K-AKT-FOXO1 signal axis, which regulates the transcriptional factors BACH1 and MAFF that can negatively regulate gene transcription of protease parts, and achieves regulation of protease activity.
    The significance of this work is that the patients with bile tube cancer can be typed by detecting the mutation of PTEN, and the treatment of protease inhibitors such as Bortezomib in patients with PTEN mutation is given, showing obvious therapeutic effect, which is expected to prolong the survival of patients.
    Because nearly 40% of bile tube cancer has PTEN mutation, and Bortzomib has been clinically used in the treatment of multiple myeloma for more than 10 years, drug safety is guaranteed, and recently a number of domestic manufacturers of Bortzomib preparations have been on the market, so this precision diagnosis and treatment strategy for many bile tube cancer patients to bring targeted treatment and extended survival of the gospel.
    in addition, the team also found that in ovarian cancer, breast cancer, prostate cancer, glioma and other malignant tumors, there are similar mechanisms of PTEN mutation and increased protease activity, the task force proposed based on PTEN mutation of the precise target treatment of bile tube cancer is expected to be extended to ovarian cancer, prostate cancer, breast cancer and other treatment, benefiting more patients.
    Oriental Hepatocholine Surgery Hospital/National Center for Hepatology and Cancer Science Wang Hongyang, Yan Yexiong and Dong Lixuan are co-authors of the paper, and graduate students Jiang Tianyi and Pan Yufei and Dr. Wan Zhenghua are co-authors.
    the research was supported by funds from the Ministry of Science and Technology, key research and development projects of the National Natural Science Foundation of China and key projects of the Shanghai Science and Technology Commission.
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