Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer

ABSTRACT

Introduction: Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer.

Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications.

Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

KEYWORDS:

• miRNAs
• drug resistance
• gastric cancer
• biomarkers
• targeted therapy

Article highlights

• Evolution of multidrug resistance (MDR) greatly weakens the efficiency of chemotherapy and the alternative treatments.

• Alterations of miRNAs expression patterns are correlated to the drug response of GC.

• Increasing studies have found that miRNAs regulate MDR via complex cellular processes in GC.

• Some key miRNAs in GC were involved in modulating drug resistance and might serve as novel biomarkers for predicting drug resistance and prognosis in GC

• Despite some challenges still lie ahead, miRNA has the potential to be a promising therapeutic target for drug resistance of GC.

• In-depth investigations about the MDR and miRNAs should be performed to establish a more effective therapy to overcome this problem.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was supported in part by grant from the National Natural Science Foundation of China [grant number 81171923], a grant from the State Key Laboratory of Cancer Biology [grant number CBSKL2014Z13] and a grant from the National Clinical Research Center for Digestive Disease [grant number 2015BAI13B07].