Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced di...Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease(locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2(HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.展开更多
Two major treatment modalities in cervical cancer are radiation therapy（RT） and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palli...Two major treatment modalities in cervical cancer are radiation therapy（RT） and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palliation.Platinum-based regimens, administered concurrently with both definitive and postoperative RT, were demonstrated to provide significant survival benefits, whereas the beneficial effect of concurrent chemoradiotherapy in later-stage disease was smaller. The role of chemotherapy in addition to RT in IB1/IIA1 cervical cancer patients not undergoing surgery remains undefined. Likewise, the role of chemotherapy in combination with postoperative RT for patients with intermediate-risk factors for recurrence has not yet been verified. The recent standard for chemoradiotherapy is cisplatin alone administered weekly. Other cisplatin-based or non-cisplatin-based regimens have not been subjected to large clinical studies. The benefits of consolidation chemotherapy after chemoradiation for locally advanced cervical cancer are still undetermined. Neoadjuvant cisplatin-based chemotherapy followed by surgery has shown survival benefits, however its role in the era of chemoradiotherapy remains unclear. The combination of cisplatin and paclitaxel is considered a standard regimen in the palliative setting. There is no standard of care for second-line systemic therapy in advanced cervical cancer.Bevacizumab combined with palliative chemotherapy（cisplatin/paclitaxel or topotecan/paclitaxel） in the first-line treatment for recurrent/metastatic cervical cancer significantly improves overall survival when compared to chemotherapy alone. The role of immunotherapy in cervical cancer remains to be established. The optimal combined modality treatment including systemic therapy for cervical tumors of non-squamous histology remains a matter of debate. Ongoing accumulation of data on genomic and proteomic characteristics provides insight into the molecular heterogeneity of cervical cancer and paves the way for developin展开更多
Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mai...Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances.展开更多
Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like m...Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.展开更多
Lung cancer is one of the most common cancer in the world.In 2018,there were over 2 million new cases of lung cancer and over 1.7 million deaths were attributed to lung cancer.Targeted therapy has emerged as an import...Lung cancer is one of the most common cancer in the world.In 2018,there were over 2 million new cases of lung cancer and over 1.7 million deaths were attributed to lung cancer.Targeted therapy has emerged as an important mean of the disease management for patients with non-small-cell lung cancer(NSCLC).Herein,we review and analyze recent literature,discuss the targeting pathways and ongoing clinical trials in lung cancer.Chemotherapy is no longer the best available treatment for all patients.Therapeutic decisions should be guided by an understanding of the molecular features of patient’s tumor tissues.The future gains will likely emerge from finding optimal ways of combining targeted therapy,immunotherapy,and chemotherapy.展开更多
The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accep...The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accepted by many as the standard of care, although debate about its overall effect on survival still exists, and rightfully so. Despite recent improvements in detection and treatment, the overall survival of patients with esophageal cancer remains lower than most solid tumors, which highlights why further advances are so desperately needed. The aim of this article is to provide a complete review of the history of esophageal cancer treatment with the addition of chemotherapy, RT, and more recently, targeted agents to the surgical management of resectable disease.展开更多
Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic ...Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.展开更多
文摘Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease(locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2(HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.
文摘Two major treatment modalities in cervical cancer are radiation therapy（RT） and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palliation.Platinum-based regimens, administered concurrently with both definitive and postoperative RT, were demonstrated to provide significant survival benefits, whereas the beneficial effect of concurrent chemoradiotherapy in later-stage disease was smaller. The role of chemotherapy in addition to RT in IB1/IIA1 cervical cancer patients not undergoing surgery remains undefined. Likewise, the role of chemotherapy in combination with postoperative RT for patients with intermediate-risk factors for recurrence has not yet been verified. The recent standard for chemoradiotherapy is cisplatin alone administered weekly. Other cisplatin-based or non-cisplatin-based regimens have not been subjected to large clinical studies. The benefits of consolidation chemotherapy after chemoradiation for locally advanced cervical cancer are still undetermined. Neoadjuvant cisplatin-based chemotherapy followed by surgery has shown survival benefits, however its role in the era of chemoradiotherapy remains unclear. The combination of cisplatin and paclitaxel is considered a standard regimen in the palliative setting. There is no standard of care for second-line systemic therapy in advanced cervical cancer.Bevacizumab combined with palliative chemotherapy（cisplatin/paclitaxel or topotecan/paclitaxel） in the first-line treatment for recurrent/metastatic cervical cancer significantly improves overall survival when compared to chemotherapy alone. The role of immunotherapy in cervical cancer remains to be established. The optimal combined modality treatment including systemic therapy for cervical tumors of non-squamous histology remains a matter of debate. Ongoing accumulation of data on genomic and proteomic characteristics provides insight into the molecular heterogeneity of cervical cancer and paves the way for developin
文摘Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances.
文摘Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.
基金The authors would like to acknowledge financial support by grants from the Shenkang Clinical Three-Year Action Plan(no.16CR3072B)the Key Project of Shanghai Health and Family Planning Commission(no.201640020)+6 种基金the Western Medicine Guiding Project of Shanghai Science and Technology Commission(no.17411967300)the Shanghai Municipal Commission of Health and Family Planning Research and Development of New Chinese Medicine and Hospital Preparations(no.2016LP029)the Shanghai Science and Technology Commission,Industry-University-Research Subproject(no.16431903200)the Shanghai Sailing Program(no.19YF1438300)the Pujiang Fostering Program of Shanghai Tenth Peoples'Hospital(no.040118024)the National Natural Science Foundation of China(no.81803090 and 81772905)the Shanghai outstanding academic leader(no.18XD1424000).
文摘Lung cancer is one of the most common cancer in the world.In 2018,there were over 2 million new cases of lung cancer and over 1.7 million deaths were attributed to lung cancer.Targeted therapy has emerged as an important mean of the disease management for patients with non-small-cell lung cancer(NSCLC).Herein,we review and analyze recent literature,discuss the targeting pathways and ongoing clinical trials in lung cancer.Chemotherapy is no longer the best available treatment for all patients.Therapeutic decisions should be guided by an understanding of the molecular features of patient’s tumor tissues.The future gains will likely emerge from finding optimal ways of combining targeted therapy,immunotherapy,and chemotherapy.
文摘The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accepted by many as the standard of care, although debate about its overall effect on survival still exists, and rightfully so. Despite recent improvements in detection and treatment, the overall survival of patients with esophageal cancer remains lower than most solid tumors, which highlights why further advances are so desperately needed. The aim of this article is to provide a complete review of the history of esophageal cancer treatment with the addition of chemotherapy, RT, and more recently, targeted agents to the surgical management of resectable disease.
文摘Despite a decrease in incidence over past decades,gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.
