Dataset Information

Gastric cancer-molecular and clinical dimensions.

ABSTRACT: Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

SUBMITTER: Wadhwa R

PROVIDER: S-EPMC3927982 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Gastric cancer-molecular and clinical dimensions.

Wadhwa Roopma R Song Shumei S Lee Ju-Seog JS Yao Yixin Y Wei Qingyi Q Ajani Jaffer A JA

Nature reviews. Clinical oncology 20130924 11

Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic target ...[more]

PMID: 24061039

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Project description:Gastric cancer was the fifth most common malignancy and the third deadliest cancer (738,000 deaths in 2018) in the world. The analysis of its molecular characteristics has been complicated by histological and intratumor heterogeneity. Furthermore, the previous studies indicate that the incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau (QTP) is one of the important global biodiversity hotspots. Here, to better understand the mechanism of gastric cancer and offer the targeted therapeutic strategies specially designed for patients in QTP, we collect tumor and blood samples from 30 primary gastric adenocarcinoma cancer patients at Qinghai Provincial People's Hospital. We discuss the clinical and molecular characteristics for these patients that have been ascribed to the unique features in this place, including high altitude (the average height above sea level is around 4,000 m), multi-ethnic groups, and the specific ways of life or habits (such as eating too much beef and mutton, have alcohol and cigarette problem, et al.). By comparing with the western gastric cancer patients collected from TCGA data portal, some unique characteristics for patients in QTP are suggested. They include high incidence in younger people, most of tumor are located in body, most of SNP are detected in chromosome 7, and the very different molecular atlas in minor ethnic groups and Han Chinese. These characteristics will provide the unprecedented opportunity to increase the efficacy for diagnosis and prognosis of gastric cancer in QTP. Furthermore, to suggest the targeted therapeutics specially designed for these 30 patients, an adapted kernel-based learning model and a compilation of pharmacogenomics data of 462 patient-derived tumor cells (PDCs) that illustrate the diverse genetic and molecular backgrounds of cancer patients, were introduced. In conclusion, our study offers a big opportunity to better understand the mechanism of gastric cancer in QTP and guide the optimal patient-tailored therapy for them.

Dataset Information

Gastric cancer-molecular and clinical dimensions.

Publications

Gastric cancer-molecular and clinical dimensions.

Similar Datasets

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