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World Journal of Gastroenterology 2014年第7期20卷 1635-1649页

作者： Michele Orditura Gennaro Galizia Vincenzo Sforza valentina gambardella Alessio Fabozzi Maria Maddalena Laterza Francesca Andreozzi Jole Ventriglia Beatrice Savastano Andrea Mabilia Eva Lieto Fortunato Ciardiello Ferdinando De Vita Division of Medical Oncology Dipartimento di MedicinaClinica e Sperimentale ‘F. Magrassi-A. Lanzara’Seconda Università degli Studi di Napoli80131 NaplesItaly Divisione di Chirurgia Oncologia Dipartimento di Scienze AnestesiologicheChirurgiche e delle EmergenzeSeconda Università degli Studi di Napoli80131 NaplesItaly

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

关键词： Gastric cancer Surgery Radiotherapy Adjuvant chemo

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Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

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World Journal of Gastroenterology 2016年第28期22卷 6345-6361页

作者： Vincenzo Sforza Erika Martinelli Fortunato Ciardiello valentina gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani Oncologia medica Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi e A. Lanzara" Seconda Università degli Studi di Napoli Department of Medical Oncology Biomedical Research Institute INCLIVA University of Valencia Department of Internal and Experimental Medicine Magrassi-Lanzara Institute of Radiology Seconda Università di Napoli Department of Pathology Istituto Nazionale Tumori "Fond. Pascale" - IRCCS Department of General and Hepato-Pancreato-Biliary Surgery S. M. Loreto Nuovo Hospital

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.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor Resistance Mutation KRAS NRAS BRAF PIK

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Clinical management of advanced gastric cancer: The role of new molecular drugs

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World Journal of Gastroenterology 2014年第40期20卷 14537-14558页

作者： Ferdinando De Vita Natale Di Martino Alessio Fabozzi Maria Maddalena Laterza Jole Ventriglia Beatrice Savastano Angelica Petrillo valentina gambardella Vincenzo Sforza Luigi Marano Annamaria Auricchio Gennaro Galizia Fortunato Ciardiello Michele Orditura Division of Medical Oncology Department of Clinical and Experimental Medicine and Surgery Second University of Naples School of Medicine 80131 Naples Italy Ⅷ General and Gastrointestinal Surgery School of Medicine Second University of Naples School of Medicine 80138 Naples Italy Divisions of Surgical Oncology Department of Clinical and Experimental Medicine and Surgery Second University of Naples School of Medicine 80131 Naples Italy

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.

关键词： Advanced gastric cancer Gastrointestinal cancer Ta

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