Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dism...Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dismal outcomes reflect the ineffectiveness of a one-size fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings.The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC.The emerging molecular classification schemes based on the genetic,epigenetic,and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner.To this end,the Cancer Genome Atlas(TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes:Epstein-Barr virus-associated tumors,microsatellite unstable tumors,genomically stable tumors,and tumors with chromosomal instability.This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies.We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.展开更多
胰腺体尾部癌症状隐匿,恶性程度高,切除率低,预后差,整体治疗有待提高.外科手术是唯一可能治愈的手段,手术治疗为核心的多学科协作的个体化治疗策略应该成为标准模式."可能切除"患者先接受新辅助治疗,再判断是否手术有助于提...胰腺体尾部癌症状隐匿,恶性程度高,切除率低,预后差,整体治疗有待提高.外科手术是唯一可能治愈的手段,手术治疗为核心的多学科协作的个体化治疗策略应该成为标准模式."可能切除"患者先接受新辅助治疗,再判断是否手术有助于提高R0切除率,改善预后.根治性顺行胰腺体尾部癌整体切除术(radical antegrade modular pancreatosplenectomy,RAMPS)手术符合肿瘤切除原则,有望成为标准的根治手术方式.腹腔镜探查术能够发现肝转移和腹腔播散,避免不必要的开腹手术.腹腔镜下胰腺体尾部癌根治术与开腹手术相比有诸多优势,但仅限于肿瘤体积较小的早期患者,肿瘤学方面的远期效果仍需验证,建议有选择地开展.联合腹腔干切除的根治性远端胰腺癌切除术(radical distal or left pancreatectomy with resection of the celiac axis,DP-CAR)适合于肝总动脉或腹腔干受侵犯但仍有条件切除的患者,需谨慎开展.胰腺体尾部癌在早期诊断、分子水平个体化治疗方面需要突破,新辅助治疗和腹腔镜手术的开展需要进一步多中心联合前瞻实验研究提供循证证据支持.展开更多
Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-l...Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.展开更多
基金supported by the National Natural Science Foundation of China(No.81502523)
文摘Gastric cancer(GC) is a highly aggressive and life-threatening malignancy.Even with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant site.The dismal outcomes reflect the ineffectiveness of a one-size fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings.The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC.The emerging molecular classification schemes based on the genetic,epigenetic,and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner.To this end,the Cancer Genome Atlas(TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes:Epstein-Barr virus-associated tumors,microsatellite unstable tumors,genomically stable tumors,and tumors with chromosomal instability.This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies.We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.
文摘胰腺体尾部癌症状隐匿,恶性程度高,切除率低,预后差,整体治疗有待提高.外科手术是唯一可能治愈的手段,手术治疗为核心的多学科协作的个体化治疗策略应该成为标准模式."可能切除"患者先接受新辅助治疗,再判断是否手术有助于提高R0切除率,改善预后.根治性顺行胰腺体尾部癌整体切除术(radical antegrade modular pancreatosplenectomy,RAMPS)手术符合肿瘤切除原则,有望成为标准的根治手术方式.腹腔镜探查术能够发现肝转移和腹腔播散,避免不必要的开腹手术.腹腔镜下胰腺体尾部癌根治术与开腹手术相比有诸多优势,但仅限于肿瘤体积较小的早期患者,肿瘤学方面的远期效果仍需验证,建议有选择地开展.联合腹腔干切除的根治性远端胰腺癌切除术(radical distal or left pancreatectomy with resection of the celiac axis,DP-CAR)适合于肝总动脉或腹腔干受侵犯但仍有条件切除的患者,需谨慎开展.胰腺体尾部癌在早期诊断、分子水平个体化治疗方面需要突破,新辅助治疗和腹腔镜手术的开展需要进一步多中心联合前瞻实验研究提供循证证据支持.
基金Supported by AIRC/Start-Up(to Giovannetti E)Istituto Toscano Tumori ITT-2011(to Caparello C,Funel N,Vasile E and Giovannetti E)+2 种基金Regione Toscana“Fas Salute”(to Funel N and Giovannetti E)Bennink Foundation(to Meijer LL,Le Large TY,Giovannetti E and Kazemier G)CCA Foundation(to Giovannetti E)
文摘Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.
