Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer.
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PMID:Targeted therapy in gastric cancer. 2570 52

Advanced gastric cancer ranks second as the global leading cause of cancer-related death and improvements in systemic chemotherapy have reached a plateau. Advanced molecular sequencing techniques help identifying patients more likely to respond to targeted agents; nevertheless we are still far from major breakthroughs. Although antiangiogenic drugs have produced notable advances, redundant pathways or mechanisms of resistance may limit their efficacy. Novel compounds have been recently developed to specifically target VEGF receptors, PlGF, FGF, MET, and angiopoietin. Ramucirumab, a monoclonal antibody specifically directed against the VEGFR-2, has emerged as a novel therapeutic opportunity. REGARD and RAINBOW were the first phase III studies to report the value of this strategy in gastric cancer patients, and other ongoing trials are testing novel antiangiogenic compounds. The aim of our review is to present the state-of-the-art of novel antiangiogenic compounds in advanced gastric cancer, underlying the biology, their mechanism of action, and their clinical results.
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PMID:Angiogenic inhibitors in gastric cancers and gastroesophageal junction carcinomas: A critical insight. 2580 Sep 76

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option.
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PMID:[Current standards in the treatment of gastric cancer]. 2640 72

Chemotherapy plays a key role in improving disease-free survival and overall survival of gastric cancer (GC); however, response rates are variable and a non-negligible proportion of patients undergo toxic and costly chemotherapeutic regimens without a survival benefit. Several studies have shown the existence of GC subtypes which may predict survival and respond differently to chemotherapy. It is also known that the expression level of chemotherapy-related and target therapy-related genes correlates with response to specific antitumor drugs. Nevertheless, these genes have not been considered jointly to define GC subtypes. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS and TOP2A) and five receptor tyrosine kinases (RTKs) (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2). We demonstrate significant heterogeneity of gene expression among GC patients and identified four GC subtypes using the expression profiles of eight genes in two co-regulation groups: chemosensitivity (BRCA1, STMN1, TYMS and TOP2A) and RTKs (EGFR, PDGFRB, VEGFR1 and VEGFR2). The results are of immediate translational value regarding GC diagnostics and therapeutics, as many of these genes are curently widely used in relevant clinical testing.
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PMID:Delineation of gastric cancer subtypes by co-regulated expression of receptor tyrosine kinases and chemosensitivity genes. 2639 73

Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer.
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PMID:Clinical utility of ramucirumab in advanced gastric cancer. 2645 Oct 83

Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.
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PMID:Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials. 2669 87

The objective of this study is to investigate antiproliferative activities against gastric cancer and anti-angiogenesis of DCT015, a novel sorafenib derivate, and potential mechanisms. The effects of DCT015 on proliferation and apoptosis in gastric cancer cells were evaluated by cytotoxicity assays, apoptosis analysis, flow cytometry analysis, and Western blotting assays. The in vivo antitumor effects were carried out in nude mice bearing gastric cancer. On the other hand, the anti-angiogenesis effects of DCT015 were measured by human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation, and Western blotting analysis. The results showed that DCT015 inhibited the proliferation, induced the morphological changes of apoptosis, and increased the apoptosis percentage, as well as increased the "sub-G1" population in gastric cancer cells. DCT015 also significantly decreased the tumor volumes and tumor weights in vivo by oral administration. Immunohistochemistry assay demonstrated that DCT015 inhibited tumor growth and neovascularization. In vitro studies found that DCT015 inhibited both MEK/ERK and PI3K/Akt signaling pathways by Western blotting assays. Moreover, DCT015 significantly inhibited VEGF-induced migration and tube formation in HUVECs. Western blotting analysis showed that DCT015 downregulated VEGF-induced VEGFR2 phosphorylation with the decreased phosphorylation of the downstream key proteins. Taken together, our findings highlight that DCT015 is a promising orally anticancer drug for treating gastric cancer.
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PMID:DCT015, a new sorafenib derivate, inhibits tumor growth and angiogenesis in gastric cancer models. 2676 19

Metastatic gastric cancer is a lethal disease characterized by a very short overall survival, underlining a critical need of new therapeutic options. Unfortunately, although several molecular targets have been investigated, only very few recently approved agents, such as trastuzumab in the HER2-positive setting and ramucirumab, led to a clinical improvement in the outcome of metastatic gastric cancer patients. VEGF (vascular endothelial growth factor) is one of the most potent angiogenic factors and is a signalling molecule secreted by many solid tumours. Since high VEGF expression is one of the characteristic features of gastric carcinomas, targeting VEGF is therefore considered as a promising therapeutic strategy for gastric cancer. In the scenario of possible new target therapies with particular regard to angiogenesis, apatinib is a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2. It is an orally-bioavailable agent currently being studied in several solid tumour types showing a promising activity in gastric cancer. Due to the recent positive results as a third line of treatment for metastatic gastric cancer patients, apatinib may be an interesting and novel type of targeted treatment for metastatic gastric cancer in several lines of therapy. In this review, we summarize the available data of apatinib, mainly focused on the clinical aspect, in advanced/metastatic gastric cancer.
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PMID:Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. 2679 19

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.
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PMID:Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application. 2688 Aug 89

Angiogenesis is a critical process in the development of tumor malignancy and occurs at various stages of tumor progression. Interleukin-8 (IL-8) is a pro-angiogenic factor produced by tumor-infiltrating macrophages that has been revealed to facilitate the development of angiogenesis in various cancers. However, whether IL-8 activates angiogenesis in gastric cancer remains unclear. The present study investigated the effect of IL-8 on the migration and canalization capacities of human umbilical vein endothelial cells (HUVECs). In addition, the protein and messenger RNA (mRNA) expression of selected angiogenesis markers, consisting of vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1 and VEGFR-2, were assessed in the HUVECs. The HUVECs were co-cultured with human gastric cancer SGC7901 cells and exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1.0 ng/ml). The migration and canalization abilities of the cells were detected by Transwell chamber and tube formation assays. Protein expression was detected using immunofluorescence and western blot analysis, and mRNA levels were assessed using reverse transcription quantitative polymerase chain reaction. The protein and mRNA levels of VEGF-A, VEGFR-1 and VEGFR-2 were measured in HUVECs cultured for 24 h. IL-8 at concentrations of 0.5, 0.8 and 1.0 ng/ml significantly promoted HUVEC cell migration (P=0.005, P=0.001 and P<0.001, respectively) and tube formation (P=0.039, P=0.003 and P<0.001, respectively). IL-8 at concentrations of 0.2, 0.5, 0.8 and 1.0 ng/ml significantly elevated the protein levels of VEGF-A (P<0.001) and VEGFR-2 (P=0.034, P<0.001, P<0.001 and P<0.001, respectively). IL-8 at concentrations of 0.8 and 1.0 ng/ml significantly elevated the protein levels of VEGF-1 (P=0.037 and P=0.002, respectively). Similarly, IL-8 at concentrations of 0.5, 0.8 and 1.0 ng/ml significantly upregulated the mRNA levels of VEGF-A (P=0.046, P=0.001 and P<0.001, respectively) and VEGFR-1 (P=0.042, P<0.001 and P<0.001, respectively). IL-8 at concentrations of 0.2, 0.5, 0.8 and 1.0 ng/ml significantly upregulated the mRNA levels of VEGFR-2 (P=0.003, P=0.005, P<0.001 and P<0.001, respectively). In conclusion, IL-8 may be a potent promoter of angiogenesis in gastric cancer.
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PMID:Interleukin-8: A potent promoter of angiogenesis in gastric cancer. 2689 88


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