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
For biliary tract carcinoma(BTC),complete surgical resection of tumor is only feasible in a minority of patients,and the treatment options for patients with unresectable or metastatic disease are limited.Advances in c...For biliary tract carcinoma(BTC),complete surgical resection of tumor is only feasible in a minority of patients,and the treatment options for patients with unresectable or metastatic disease are limited.Advances in cancer immunology have led to identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in BTC.This has also facilitated development of immunotherapy that focuses on enhancing the immune system against biliary tumors.This includes peptide- and dendritic cell-based vaccines that stimulate in-vivo immune responses against tumorspecific antigens.Adoptive immunotherapy,which entails the ex-vivo expansion of tumor-infiltrating immune cells for subsequent reintroduction,and cytokinebased therapies have been developed in BTC.Clinical studies indicate that this type of therapy is generally well tolerated.Combination therapy with dendritic cell-based vaccines and adoptive immunotherapy has shown particularly good potential.Emerging strategies through discovery of novel antigen targets and by reversal of tumor-associated immunosuppression are expected to improve the efficacy of immunotherapy in BTC.Collaborative efforts by integration of targeted immunotherapeutics with molecular profiling of biliary tumor will hopefully make a positive impact on advancing towards the goal of developing precision treatment of patients with this highly lethal disease.展开更多
Despite various advances in cancer research,the incidence and mortality rates of malignant diseases have remained high.Accurate risk assessment,prevention,detection,and treatment of cancer tailored to the individual a...Despite various advances in cancer research,the incidence and mortality rates of malignant diseases have remained high.Accurate risk assessment,prevention,detection,and treatment of cancer tailored to the individual are major challenges in clinical oncology.Artificial intelligence(AI),a field of applied computer science,has shown promising potential of accelerating evolution of healthcare towards precision oncology.This article focuses on highlights of the application of data-driven machine learning(ML)and deep learning(DL)in translational research for cancer diagnosis,prognosis,treatment,and clinical outcomes.MLbased algorithms in radiological and histological images have been demonstrated to improve detection and diagnosis of cancer.DL-based prediction models in molecular or multi-omics datasets of cancer for biomarkers and targets enable drug discovery and treatment.ML approaches combining radiomics with genomics and other omics data enhance the power of AI in improving diagnosis,prognostication,and treatment of cancer.Ethical and regulatory issues involving patient confidentiality and data security impose certain limitations on practical implementation of ML in clinical oncology.However,the ultimate goal of application of AI in cancer research is to develop and implement multi-modal machine intelligence for improving clinical decision on individualized management of patients.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.
文摘For biliary tract carcinoma(BTC),complete surgical resection of tumor is only feasible in a minority of patients,and the treatment options for patients with unresectable or metastatic disease are limited.Advances in cancer immunology have led to identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in BTC.This has also facilitated development of immunotherapy that focuses on enhancing the immune system against biliary tumors.This includes peptide- and dendritic cell-based vaccines that stimulate in-vivo immune responses against tumorspecific antigens.Adoptive immunotherapy,which entails the ex-vivo expansion of tumor-infiltrating immune cells for subsequent reintroduction,and cytokinebased therapies have been developed in BTC.Clinical studies indicate that this type of therapy is generally well tolerated.Combination therapy with dendritic cell-based vaccines and adoptive immunotherapy has shown particularly good potential.Emerging strategies through discovery of novel antigen targets and by reversal of tumor-associated immunosuppression are expected to improve the efficacy of immunotherapy in BTC.Collaborative efforts by integration of targeted immunotherapeutics with molecular profiling of biliary tumor will hopefully make a positive impact on advancing towards the goal of developing precision treatment of patients with this highly lethal disease.
文摘Despite various advances in cancer research,the incidence and mortality rates of malignant diseases have remained high.Accurate risk assessment,prevention,detection,and treatment of cancer tailored to the individual are major challenges in clinical oncology.Artificial intelligence(AI),a field of applied computer science,has shown promising potential of accelerating evolution of healthcare towards precision oncology.This article focuses on highlights of the application of data-driven machine learning(ML)and deep learning(DL)in translational research for cancer diagnosis,prognosis,treatment,and clinical outcomes.MLbased algorithms in radiological and histological images have been demonstrated to improve detection and diagnosis of cancer.DL-based prediction models in molecular or multi-omics datasets of cancer for biomarkers and targets enable drug discovery and treatment.ML approaches combining radiomics with genomics and other omics data enhance the power of AI in improving diagnosis,prognostication,and treatment of cancer.Ethical and regulatory issues involving patient confidentiality and data security impose certain limitations on practical implementation of ML in clinical oncology.However,the ultimate goal of application of AI in cancer research is to develop and implement multi-modal machine intelligence for improving clinical decision on individualized management of patients.
