Study of response to treatment of mek inhibitor in gastric cancer patients with mutation in the kras gene

Mehrasa Asghari,1,* Pedram asghari,2

1. Department of Biology, Faculty of Basic Sciences, SCIENCE AND RESERCH Branch, Islamic Azad University, Tehran, Iran
2. Department of Biology, Faculty of Basic Sciences, SCIENCE AND RESERCH Branch, Islamic Azad University, Qaemshahr, Iran

Abstract

Introduction

Gastric cancer is the second leading cause of death from cancer worldwide. the death rates increasing in asian countries such as iran. the chemotherapy is one of the ways to treat gastric cancer. activating ras and also kras mutation contributes to the induction of gastric cancer. recent studies suggest that patients with mutated or amplified kras gene are better response to chemotherapy for mek inhibitors. the aim of this study is to evaluate the response of mek inhibitor in gastric cancer patients with mutations in the kras gene.

Methods

In this study, related articles were searched for the response to treatment with mek inhibitors in gastric cancer patients with mutations in kras gene using appropriate keywords in electronic databases including springer, web of science, medline, and science direct.

Results

Various articles have highlighted the relationship between enhancement in the kras mutation, activation of the kras signaling pathway and cell proliferation in gastric cancer. in a study, the overexpression of the kras gene in the signet-ring cell carcinoma (srcc) has been observed. studies have shown that gastric cancer can be controlled by mek inhibitors (selumetinib). mek inhibitors that also function in the mapk pathway suppresses mapk signaling in models harboring active kras gene. the use of mek inhibitors and docetaxel in chemotherapy had beneficial and enduring effects on gastric cancer patients with mutated ras genes, especially in a group of patients who have mutated or amplified kras. studies have identified shp2 as a mediator for body adaptation to treatment with mek inhibitor in human tumors. allosteric inhibition of shp2 enhances the antitumor effect of mek inhibitor treatment and inhibiting them will increase the inhibitory effect of mek on kras-induced cancers. in a study, when administered together, the mek inhibitors and shp2, they could effectively inhibit kras-amplified gastric tumor growth in both cell culture experiments and animal models. only two studies examined the frequency of kras gene in gastric cancer patients in iran, one of which is the research we have done. in this study, the frequency of codon-12 and 13 mutations has been investigated in the kras gene in patients with gastric cancer in the north of iran. in this review, it can be concluded that in patients with gastric cancer that is used chemotherapy for their treatment, first, it is necessary to examine the changes in the kras gene and then use mek inhibitors in their treatment to obtain better and more effective results.

Conclusion

Clinically, it is important to use a precise and effective method that reflects ras activity to classify patients who can benefit from treatment with a mek inhibitors (selumetinib) in gastric cancer. our study showed that the use of mek inhibitors for treating gastric cancer patients with kras gene mutations could be helpful. therefore, with more research and targeted therapies, the chances of success in treating patients with gastric cancer can be increased.

Keywords

Gastric cancer, mek inhibitors, kras gene mutations