Abstract
Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been characterized for GC are provided. In particular, the most recent molecular classification of GC and alterations identified in relevant signaling pathways, including ErbB, VEGF, PI3K/AKT/mTOR, and HGF/ MET signaling pathways, are described, as well as inhibitors of these pathways. An overview of the completed and active clinical trials related to these signaling pathways are also summarized. Finally, insights regarding emerging stem cell pathways are described, and may provide additional novel markers for the development of therapeutic agents against GC. The development of more effective agents and the identification of biomarkers that can be used for the diagnosis, prognosis, and individualized therapy for GC patients, have the potential to improve the efficacy, safety, and cost-effectiveness for GC treatments.
Highlights
Gastric cancer (GC) is an important public health problem worldwide due to its high incidence and mortality
We review management strategies for cases of advanced stage GC, current knowledge regarding the molecular classification of GC, and we discuss the emerging role of signaling pathways that are affected in GC and that provide the identification of new therapeutic targets for this disease
Emerging data from high-throughput technologies have provided valuable insight into the molecular classification and intracellular pathways that are relevant to GC, and this facilitates the development of novel strategies for treating GC
Summary
Gastric cancer (GC) is an important public health problem worldwide due to its high incidence and mortality. The addition of CRT did not benefit GC patients in the chemotherapy alone group, with a 3-year disease-free survival (DFS) rate for the XP/XRT/XP group versus the XP group being 78.2% and 74.2%, respectively (P = 0.0862). In the Asian group Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC), S-1, an oral fluoropyrimidine chemotherapy agent, was investigated [14] In this randomized study of 1,059 patients with stage II-III GC, the 3-year OS rate was 80% versus 70% for surgery alone. In a meta-analysis of 35 clinical studies and www.impactjournals.com/oncotarget a total of 5,726 patients that was performed to evaluate chemotherapy for cases of advanced stage GC in 2010, a significant benefit in OS was observed for the group that received chemotherapy versus best supportive care (HR = 0.37, 95% CI: 0.24-0.55) [16]. An increasing number of genetic abnormalities have been identified over the past couple decades, thereby providing additional insight into the molecular alterations that lead to the development of GC subtypes
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