Genomic landscape of gastric cancer: molecular classification and potential targets

Abstract

Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, RhoA-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future. gastric cancer, chromatin remodeling, RhoA, p53, receptor tyrosine kinase, DNA methylation Citation:

Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology

“…The MLH1 protein, a product of the MLH1 gene, plays an essential role in DNA mismatch repair and is responsible for fixing errors that occur during DNA replication. MSI-positive GCs are often associated with activation of the epidermal growth factor receptor (EGFR) and PI3K pathways [ 27 ].…”

“…The most frequently mutated gene in GC is TP53 . This mutation was observed in approximately 40% of GC cases [ 27 ]. TP53 is a tumor suppressor protein, which plays an important role in cell cycle arrest, metabolism, senescence, apoptosis and DNA repair.…”

Ten years of achievements in biological and medical sciences

“…His team has been focused on basic research to understand physiological functions of G-protein coupled receptors, and translational research to discover innovative drugs by targeting critical cell signaling pathways in cancers. Dr. Mingyao Liu and his colleagues summarize molecular targets of human gastric cancer based on collaborative sequencing data (Guo et al, 2017), discover a novel angiogenesis inhibitor and set up pharmacokinetic platform to evaluate compounds' activity on metabolic enzymes (Lu et al, 2017). Besides the above research groups, there are other groups in IBMS that focus on structure biology, immunology, synthetic biology and functional proteomics.…”

An association between single nucleotide polymorphisms in the promoter region of alcohol dehydrogenase 1B and the risk of developing colorectal carcinoma in the Chinese Han population

“…相关研究表明, 在不同 人种中遗传因素对结直肠癌的发生发展均发挥着重 要作用 [3~5] . 流行病学研究认为酒精代谢异常与多种肿瘤的 发生相关, 例如, 口腔癌、咽癌、喉癌、食道癌、 肝癌、结直肠癌和乳腺癌等 [6,7] . 乙醇脱氢酶(alcohol dehydrogenase, ADH)和乙醛脱氢酶(aldehyde dehydro-genase, ALDH)是人体内代谢酒精的主要酶类 [8] .…”