Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more...Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome;therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective;having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.展开更多
Ductal carcinoma in situ （DCIS） is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of mult...Ductal carcinoma in situ （DCIS） is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immuno-histochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment. However, there are no available targeted therapies for patients with basal-like DCIS （BL-DCIS） tumors due to their frequent lack of endocrine receptors and HER2 amplification, rendering them potentially susceptible to recurrence. Moreover, multiple lines of evidence suggest that DCIS is a non-obligate precursor of invasive breast carcinoma. This raises the possibility that targeting precursor BL-DCIS is a promising strategy to prevent BL-DCIS patients from the development of invasive basal-like breast cancer. An accumulating body of evidence demonstrates the existence of cancer stem-like cells （CSCs） in BL-DCIS, which potentially determine the features of BL-DCIS and their ability to progress into invasive cancer. This review encompasses the current knowledge in regard to the characteristics of BL-DCIS, identifcation of CSCs, and their biological properties in BL-DCIS. We summarize recently discovered relevant molecular signaling alterations that promote the generation of CSCs in BL-DCIS and the progression of BL-DCIS to invasive breast cancer, as well as the infuence of the tissue microenvironment on CSCs and the invasive transition. Finally, we discuss the translational implic-ations of these fndings for the prognosis and prevention of BL-DCIS relapse and progression.展开更多
Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this ca...Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. Recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be determined.For many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a signifcant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.展开更多
文摘Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome;therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective;having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.
基金Supported by The National Cancer Institute(NCI)of National Institutes of Health(NIH)of the United States of America to Zhou Q,Nos.5R01CA157779-03 and 5R01CA163820-04
文摘Ductal carcinoma in situ （DCIS） is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immuno-histochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment. However, there are no available targeted therapies for patients with basal-like DCIS （BL-DCIS） tumors due to their frequent lack of endocrine receptors and HER2 amplification, rendering them potentially susceptible to recurrence. Moreover, multiple lines of evidence suggest that DCIS is a non-obligate precursor of invasive breast carcinoma. This raises the possibility that targeting precursor BL-DCIS is a promising strategy to prevent BL-DCIS patients from the development of invasive basal-like breast cancer. An accumulating body of evidence demonstrates the existence of cancer stem-like cells （CSCs） in BL-DCIS, which potentially determine the features of BL-DCIS and their ability to progress into invasive cancer. This review encompasses the current knowledge in regard to the characteristics of BL-DCIS, identifcation of CSCs, and their biological properties in BL-DCIS. We summarize recently discovered relevant molecular signaling alterations that promote the generation of CSCs in BL-DCIS and the progression of BL-DCIS to invasive breast cancer, as well as the infuence of the tissue microenvironment on CSCs and the invasive transition. Finally, we discuss the translational implic-ations of these fndings for the prognosis and prevention of BL-DCIS relapse and progression.
文摘Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. Recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be determined.For many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a signifcant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.
