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Molecular-targeted therapy toward precision medicine for gastrointestinal caner:Current progress and challenges

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World Journal of Gastrointestinal Oncology 2021年第5期13卷 366-390页

作者： Tasuku Matsuoka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of MedicineOsaka 545-8585Japan

Gastrointestinal(GI)cancer remains the deadliest cancer in the *** current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery,and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI *** is wellestablished evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies,which should routinely be incorporated into treatment strategies for GI *** potential therapeutic targets involve the PI3K/AKT pathway,tumor growth factor-βpathway,mesenchymal-epithelial transition pathway,WNT pathway,poly(ADP-ribose)polymerase,and immune *** clinical trials assessing the agents of targeted therapy are underway and have presented promising and thoughtprovoking *** the development of molecular biology techniques,we can identify more targetable molecular alterations in larger patient populations with GI *** these molecules will allow us to reach the goal of precision medicine and improve the outcomes of patients with GI cancer.

关键词： Gastrointestinal cancer Esophageal cancer Gastric cancer Colorectal cancer Targeted therapy Precision medicine

Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer

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World Journal of Gastroenterology 2016年第8期22卷 2415-2423页

作者： masakazu yashiro Tasuku Matsuoka Department of Surgical Oncology Osaka City University Graduate School of Medicine Oncology Institute of Geriatrics and Medical Science Osaka City University Graduate School of Medicine

Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.

关键词： Fibroblast growth factor receptor Gastric cancer Signaling pathway Targeted therapy

Rho/ROCK signaling in motility and metastasis of gastric cancer

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World Journal of Gastroenterology 2014年第38期20卷 13756-13766页

作者： Tasuku Matsuoka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of Medicine

Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have revealed that the Rho/Rho-associated protein kinases(ROCK) pathway plays a critical role in the regulation of cancer cell motility and invasion. In addition,the Rho/ROCK pathway plays important roles in invasion and metastasis on the basis of its predominant function of cell cytoskeletal regulation in gastric cancer. According to the current understanding of tumor motility,there are two modes of tumor cell movement:mesenchymal and amoeboid. In addition,cancer cell movement can be interchangeable between the mesenchymal and amoeboid movements under certain conditions. Control of cell motility through the actin cytoskeleton creates the potential for regulating tumor cell metastasis. In this review we discuss Rho GTPases and ROCK signaling and describe the mechanisms of Rho/ROCK activity with regard to motility and metastasis in gastric *** addition,we provide an insight of the therapeutic potential of targeting the Rho/ROCK pathway.

关键词： RhoGTPases Rho-associated protein kinases Gastric cancer Motility Metastasis

Novel biomarkers for early detection of gastric cancer

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World Journal of Gastroenterology 2023年第17期29卷 2515-2533页

作者： Tasuku Matsuoka masakazu yashiro Molecular Oncology and Therapeutics Osaka Metropolitan University Graduate School of MedicineOsaka 5458585Japan

Gastric cancer(GC)remains a leading cause of cancer-related death *** than half of GC cases are diagnosed at an advanced stage due to its lack of early *** is a heterogeneous disease associated with a number of genetic and somatic *** detection and effective monitoring of tumor progression are essential for reducing GC disease burden and *** current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number of treatable cancers:However,these approaches are invasive,costly,and ***,novel molecular noninvasive tests that detect GC alterations seem to be more sensitive and specific compared to the current *** technological advances have enabled the detection of blood-based biomarkers that could be used as diagnostic indicators and for monitoring postsurgical minimal residual *** biomarkers include circulating DNA,RNA,extracellular vesicles,and proteins,and their clinical applications are currently being *** identification of ideal diagnostic markers for GC that have high sensitivity and specificity would improve survival rates and contribute to the advancement of precision *** review provides an overview of current topics regarding the novel,recently developed diagnostic markers for GC.

关键词： Gastric cancer Diagnostic biomarkers Early detection Liquid biopsy

Biomarkers of gastric cancer:Current topics and future perspective

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World Journal of Gastroenterology 2018年第26期24卷 2818-2832页

作者： Tasuku Matsuoaka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of MedicineOsaka 545-8585Japan Oncology Institute of Geriatrics and Medical Science Osaka City University Graduate School of MedicineOsaka 545-8585Japan

Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.

关键词： Biomarkers Ccancer diagnosis Prognostic marker Predictive marker Gastric cancer

Precision medicine for gastrointestinal cancer:Recent progress and future perspective

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World Journal of Gastrointestinal Oncology 2020年第1期12卷 1-20页

作者： Tasuku Matsuoka masakazu yashiro Department of Gastroenterological Surgery Osaka City University Graduate School of MedicineOsaka 5458585Japan Oncology Institute of Geriatrics and Medical Science Osaka City University Graduate School of MedicineOsaka 5458585Japan

Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate *** significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal *** is an urgent need for new diagnostic and therapeutic *** technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI *** we review the application and status of precision medicine in GI *** of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with *** the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI *** the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted *** progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.

关键词： Gastrointestinal cancer Esophageal cancer Gastric cancer Colorectal cancer Precision medicine Liquid biopsy Gene panel Precision surgery Biomarkers

Recent advances in the HER2 targeted therapy of gastric cancer

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World Journal of Clinical Cases 2015年第1期3卷 42-51页

作者： Tasuku Matsuoka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of Medicine Osaka 545-8585 Japan Oncology Institute of Geriatrics and Medical Science Osaka City University Graduate School of Medicine Osaka 545-8585 Japan

Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.

关键词： Human epidermal growth factor receptor 2 Gastric cancer Targeting therapy Trastuzumab

Molecular targets for the treatment of pancreatic cancer:Clinical and experimental studies

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World Journal of Gastroenterology 2016年第2期22卷 776-789页

作者： Tasuku Matsuoka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of MedicineOsaka 545-8585Japan Oncology Institute of Geriatrics and Medical Science Osaka City University Graduate School of MedicineOsaka 545-8585Japan

Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future.

关键词： Pancreatic cancer Targeted therapy Tyrosinekinase inhibitors Microenvironment Cancer stem cell

Significance of peritoneal lavage cytology based on genetic signatures in gastric cancer

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 75-87页

作者： Tasuku Matsuoka masakazu yashiro Department of Surgical Oncology Osaka City University Graduate School of Medic ineOsaka 545-8585Japan Molecular Oncology and Therapeutics Osaka City University Graduate School of MedicineOsaka 545-8585Japan

Perit on eal metastasis is the most comm on patter n of recurre nee and the most freque nt cause of death after surgery in patie nts with gastric can *** on eal free can cer cells dissem in ated from the primary lesi on site have bee n con sidered the main cause of perit on eal *** on eal lavage cytological exam in ati on(PLC)has bee n show n to be an in depe ndent predictor of gastric cancer relapse after curative resection and poor overall ***,the conventional cytological examinations have high rates of false-positive and false-negative *** improve the sensitivity,molecular-based methods using reverse transcriptase polymerase chain reaction have been developed for detecting cancer cells in peritoneal wash fluids of patients with gastric *** performed a PubMed search for articles describing PLC in gastric can *** nt articles were reviewed and data on available outcomes *** cli nical roles and attributes of PLC in gastric can cer were reviewed,and its future applicati on to this disease is discussed.

关键词： Gastric cancer peritoneal lavage cytology genetic detection reverse transcriptase polymerase chain reaction carcinoembryonic antigen