The primary malignancies of the biliary tract, cholangio-carcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates...The primary malignancies of the biliary tract, cholangio-carcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma(BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.展开更多
Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders.Metabolomics provides a comprehensive understanding of metabolism in biological systems.With advanced analytical techniq...Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders.Metabolomics provides a comprehensive understanding of metabolism in biological systems.With advanced analytical techniques,metabolomics exhibits unprecedented significant value in basic drug research,including understanding disease mechanisms,identifying drug targets,and elucidating the mode of action of drugs.More importantly,metabolomics greatly accelerates the drug development process by predicting pharmacokinetics,pharmacodynamics,and drug response.In addition,metabolomics facilitates the exploration of drug repurposing and drug-drug interactions,as well as the development of personalized treatment strategies.Here,we briefly review the recent advances in technologies in metabolomics and update our knowledge of the applications of metabolomics in drug research and development.展开更多
文摘The primary malignancies of the biliary tract, cholangio-carcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma(BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.
基金supported by Tsinghua University Spring Breeze Fund(2021Z99CFY031)National Natural Science Foundation of China(32150024 and 92057209)supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ16-YQ-046 and ZZ16-ND10-13,China)。
文摘Emerging evidence has demonstrated the vital role of metabolism in various diseases or disorders.Metabolomics provides a comprehensive understanding of metabolism in biological systems.With advanced analytical techniques,metabolomics exhibits unprecedented significant value in basic drug research,including understanding disease mechanisms,identifying drug targets,and elucidating the mode of action of drugs.More importantly,metabolomics greatly accelerates the drug development process by predicting pharmacokinetics,pharmacodynamics,and drug response.In addition,metabolomics facilitates the exploration of drug repurposing and drug-drug interactions,as well as the development of personalized treatment strategies.Here,we briefly review the recent advances in technologies in metabolomics and update our knowledge of the applications of metabolomics in drug research and development.
