Lifestyles, genetics, and future perspectives on gastric cancer in east Asian populations.
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ABSTRACT:
SUBMITTER: Katoh H
PROVIDER: S-EPMC8384627 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase?I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.
| S-EPMC4716053 | biostudies-literature
Project description:Laparoscopic gastrectomy has been widely accepted as a standard alternative for the treatment of early-stage gastric adenocarcinoma because of its favorable short-term outcomes. Although controversies exist, such as establishing clear indications, proper preoperative staging, and oncologic safety, experienced surgeons and institutions have applied this approach, along with various types of function-preserving surgery, for the treatment of advanced gastric cancer. With technical advancement and the advent of state-of-the-art instruments, indications for laparoscopic gastrectomy are expected to expand as far as locally advanced gastric cancer. Laparoscopic gastrectomy appears to be promising; however, scientific evidence necessary to generalize this approach to a standard treatment for all relevant patients and care providers remains to be gathered. Several multicenter, prospective randomized trials in high-incidence countries are ongoing, and results from these trials will highlight the short- and long-term outcomes of the approach. In this review, we describe up-to-date findings and critical issues regarding laparoscopic gastrectomy for gastric cancer.
| S-EPMC4716072 | biostudies-literature
Project description: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.
| S-EPMC4768187 | biostudies-literature
Project description:BACKGROUND:Lung cancer (LC) is the leading cause of cancer-related death in Eastern Asia. The prognosis of LC highly depends on tumor stages and early detection could substantially reduce LC mortality. Accumulating evidence suggested that circulating miRNAs in plasma or serum may have applications in early LC detection. We thus conducted a systematic literature review on the diagnostic value of miRNAs markers for LC in East Asian populations. METHODS:PubMed and ISI Web of Knowledge were searched to retrieve relevant articles published up to 17 September 2018. Information on study design, population characteristics, investigated miRNAs and diagnostic accuracy (including sensitivity, specificity and area under the curve (AUC)) were independently extracted by two reviewers. RESULTS:Overall, 46 studies that evaluated a total of 88 miRNA markers for LC diagnosis in East Asian populations were identified. Sixteen of the 46 studies have incorporated individual miRNA markers as panels (with 2?20 markers). Three promising miRNA panels with ?90% sensitivity and ?90% specificity were discovered, two of which were externally validated. Diagnostic performance of circulating miRNAs in East Asian populations was comparable to previously summarized performance in Western populations. Forty-four miRNAs were reported in both populations. No major differences in diagnostic performance by ethnicity of the same miRNA was observed. CONCLUSIONS:Circulating miRNAs or miRNA panels, possibly in combination with other promising molecular markers including epigenetic and genetic markers, may be promising candidates for noninvasive LC early detection. However, large studies with samples collected prospectively in true screening settings are required to validate the promising markers or marker panels.
| S-EPMC6468694 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-06-10 | GSE152200 | GEO
Project description:Germline and environmental effects on the development of gastric cancers (GC) and their ethnic differences have been poorly understood. Here, we performed genomic-scale trans-ethnic analysis of 531 GCs (319 Asian and 212 non-Asians). There was one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, almost all of which were attributable to alcohol intake behavior, smoking habit, and Asian-specific defective ALDH2 allele. Alcohol-related GCs have low mutation burden and characteristic immunological profiles. In addition, we found frequent (7.4%) germline CDH1 variants among Japanese GCs, most of which were attributed to a few recurrent single-nucleotide variants shared by Japanese and Koreans, suggesting the existence of common ancestral events among East Asians. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective ALDH2 allele or to CDH1 variants. These results revealed uncharacterized impacts of germline variants and lifestyles in the high incidence areas.
| S-EPMC7202881 | biostudies-literature
Project description:BackgroundThe highest incidence of gastric cancer is in East Asia, corresponding to a high prevalence of Helicobacter pylori (H. pylori), yet other regions with a similarly high prevalence of H. pylori have lower cancer rates. Foreign-born persons who immigrate to the United States are thought to remain at high-risk for gastric cancer, but this has not been confirmed by large population-based studies.MethodsWe evaluated total and foreign-born populations in metropolitan statistical areas (MSAs). Cardia and non-cardia gastric adenocarcinomas diagnosed between 2006 and 2016 were identified using the Surveillance, Epidemiology, and End Results Program. Generalized linear regression models determined whether the incidence of gastric cancer in each MSA was associated with specific foreign-born populations.ResultsAmong 32 MSAs, we identified 55,937 patients with gastric adenocarcinoma. A greater percentage of Eastern European-born individuals in an MSA was associated with a higher incidence of cardia cancers (coefficient 1.32, P=0.02). Evaluating Asian-born populations alone, a greater percentage of Japanese-born individuals was associated with a higher incidence of non-cardia cancers (coefficient 2.48, P=0.03), whereas Korean or Chinese origin was not associated with a significantly higher risk.ConclusionsOn a population level, a greater percentage of Eastern European-born individuals is associated with a higher incidence of cardia gastric adenocarcinomas. Among Asian-born individuals, Korean or Chinese origin was not associated with a significantly higher risk, but a greater percent of persons born in other Asian countries, including Japan, was associated with a higher incidence of non-cardia gastric adenocarcinomas in an MSA.
| S-EPMC8375647 | biostudies-literature
Project description:Gastric cancer (GC) represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year. In the last decade, the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treatment options for advanced GC and granted better survival expectations to the patients. At the same time, global efforts have been undertaken to investigate in detail the genomic and epigenomic heterogeneity of this disease, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling. Nonetheless, several randomized studies aimed at exploring new innovative agents, such as immune checkpoint inhibitors, failed to demonstrate clinically meaningful survival advantages. Therefore, it is essential to further improve the molecular characterization of GC subgroups in order to provide researchers and medical oncologists with new tools for patients' selection and stratification in future clinical development programs and subsequent trials. The aim of the present manuscript is to provide a global overview of the recent molecular classifications from The Cancer Genome Atlas and the Asian Cancer Research Group and to present key promising developments in the field of immunotherapy and targeted therapies in metastatic GC.
| S-EPMC6801189 | biostudies-literature
Project description:Gastric cancer (GC) is the fifth-most common cancer worldwide and an important cause of cancer-related-death. The growing knowledge of its molecular pathogenesis has shown that GC is not a single entity, but a constellation of different diseases, each with its own molecular and clinical characteristics. Currently, surgery represents the only curative approach for localized GC, but only 20% of patients (pts) showed resectable disease at diagnosis and, even in case of curative resection, the prognosis remains poor due to the high rate of disease relapse. In this context, multimodal perioperative approaches were developed in western and eastern countries in order to decrease relapse rates and improve survival. However, there is little consensus about the optimal treatment for non-metastatic GC. In this review, we summarize the current status and future developments of perioperative chemotherapy in resectable GC, attempting to find clear answers to the real problems in clinical practice.
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Project description:Gastric cancer, with high morbidity and mortality rates, is one of the most heterogeneous tumors. Radical gastrectomy and postoperative chemotherapy are the standard treatments. However, the safety and efficacy of neoadjuvant therapy (NAT) need to be confirmed by many trials before implementation, creating a bottleneck in development. Although clinical benefits of NAT have been observed, a series of problems remain to be solved. Before therapy, more contributing factors should be offered for choice in the intended population and ideal regimens. Enhanced computed tomography (CT) scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors (RECIST), yet CT scanning results sometimes differ from pathological responses. After NAT, the appropriate time for surgery is still empirically defined. Our review aims to discuss the abovementioned issues regarding NAT for GC, including indications, selection of regimens, lesion assessment and NAT-surgery interval time.
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