The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the sec...The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance展开更多
The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening ...The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience.展开更多
The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6...The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them.展开更多
Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States.Surgery represents...Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States.Surgery represents the main approach for this disease but,notwithstanding the advances in surgical techniques,we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates.Despite the development of new drugs has significantly improved the effectiveness of chemothera-py,the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor.Recently,several molecular target agents have been investigated;in particular,trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients.New molecules targeting vascular epithelial growth factor,mammalian target of rapamycin,and anti hepatocyte growth factor-c-Met pathway are also under investigation,with interesting results.Anyway,it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results.In this paper we review the actual"scenario"of targeted treatments,also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma,discussing their efficacy and potential applications in clinical practice.展开更多
The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entiti...The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of HCC.Among all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression.HH plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal progenitors.The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development.HH activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells.High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome.In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype.展开更多
In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer(m CRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients...In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer(m CRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with m CRC. In this review, we describe approved targeted therapies for the management of metastatic m CRC and discuss new candidate targets on the horizon.展开更多
文摘The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance
文摘The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience.
文摘The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them.
文摘Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States.Surgery represents the main approach for this disease but,notwithstanding the advances in surgical techniques,we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates.Despite the development of new drugs has significantly improved the effectiveness of chemothera-py,the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor.Recently,several molecular target agents have been investigated;in particular,trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients.New molecules targeting vascular epithelial growth factor,mammalian target of rapamycin,and anti hepatocyte growth factor-c-Met pathway are also under investigation,with interesting results.Anyway,it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results.In this paper we review the actual"scenario"of targeted treatments,also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma,discussing their efficacy and potential applications in clinical practice.
文摘The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma(HCC)is poor because there are few treatment options.Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis,proliferation and progression of HCC.Among all of the pathways that are involved in the development of HCC,Hedgehog(HH)signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression.HH plays a physiological role in embryogenesis,through the induction of the differentiation of hepatocytes from endodermal progenitors.The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development.HH activation sustains the subpopulation of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC,and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells.High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome.In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth,metastasis and a mesenchymal phenotype.
文摘In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer(m CRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with m CRC. In this review, we describe approved targeted therapies for the management of metastatic m CRC and discuss new candidate targets on the horizon.
