Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagno...Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.展开更多
Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovaria...Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies.The cell-of-origin of this subtype of ovarian cancer is unknown.While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous features.Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.展开更多
文摘Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.
基金supported by the National Cancer Institute/the National Institute of Health(1R01CA197976,1R01CA201500)Vincent Memorial Hospital Foundation+6 种基金the Vincent Center for Reproductive Biologythe Olson Center for Women’s HealthUniversity of Nebraska Medical Center Graduate Studies Fellowshipthe Fred&Pamela Buffett Cancer Center(LB595)Colleen’s Dream FoundationMarsha Rivkin Center for Ovarian Cancer Research(the Barbara Learned Bridge Funding Award)the Co BRE grant from the Nebraska Center for Cellular Signaling/the National Institute of General Medical Science/the National Institute of Health(5P30GM106397)。
文摘Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies.The cell-of-origin of this subtype of ovarian cancer is unknown.While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous features.Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.
