Cellular and Molecular Mechanisms of Chemoresistance for Gastric Cancer - Review

Sep 21, 2026

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Gastric cancer is a prevalent malignancy in the digestive tract, and chemotherapy is essential to its comprehensive management. Long-term clinical benefit is undermined by chemoresistance, which drives treatment failure and contributes to tumor recurrence, metastasis, and patient death. This review analyzes the detailed cellular and molecular mechanisms responsible for chemoresistance in gastric cancer, with the goal of clarifying therapeutic targets and improving patient prognosis.

LanguageEnglish

CategoryResearch & Report

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Pages10

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Introduction

Cellular and Molecular Mechanisms of Chemoresistance for Gastric Cancer

Drug Efflux Mediated by Membrane Proteins

International Journal of General Medicine Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Cellular and Molecular Mechanisms of Chemoresistance for Gastric Cancer Zonglin Li 1 , *, Xingming Shu 1 , *, Xin Liu 1 , Qiuyun Li 2 , Yifu Hu2 , Bingbing Jia2 , Min Song 3 1Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Grade 2023, Clinical Medicine College, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China *These authors contributed equally to this work Correspondence: Min Song, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +8615883059785, Email [songminlele2007@126.com](songminlele2007@126.com) | Abstract: Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.
Keywords: gastric cancer, chemoresistance, cellular mechanisms, molecular mechanisms | | --- | | Introduction
Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract and seriously threatens human life and health. According to statistics, there were more than 1,089,103 new GC cases and 768,793 GC-induced deaths in 2020 worldwide, ranking fifth in morbidity and fourth in mortality among all cancer types.1 In China, more than 509,421 new GC cases and 400,415 GC-induced deaths were recorded in 2022, ranking third in both morbidity and mortality among all cancer types.2 At present, surgery is still the most important treatment for resectable GC.3 Although comprehensive and individualized treatment based on surgery, chemoradiotherapy, targeted therapy and immunotherapy have been widely used in the treatment of GC, the overall efficacy is still not satisfactory. The 5-year survival rate of GC patients is only about 44.5%, and for patients with distant metastasis, it is only about 8.4% .4 Chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for GC patients to benefit steadily from chemotherapy in the long term. According to related reports, the proportion of GC patients resistant to chemotherapy isabout 46% to 80% .5,6 For GC, chemotherapy regimens including XELOX (oxaliplatin plus capecitabine), SOX (S-1 plus oxaliplatin) and FOLFOX (oxaliplatin plus leucovorin and 5-fluorouracil) have been widely used in the clinical treatment.7,8 But their efficacy is relatively limited and more than 95% GC patients fail chemotherapy with the progression of chemoresistance, which ultimately leads to tumor recurrence, metastasis, and patient death.9 Chemoresistance of GC cells can be divided into primary drug resistance and acquired drug resistance, primary drug resistance means that GC cells possess genetic characteristics of natural drug resistance to various chemotherapeutic drugs, while acquired drug resistance refers to drug resistance produced by GC cells after long-term or repeated action of chemotherapeutic drugs.10 Currently, most information about chemoresistance of GC cells is obtained from vitro experimental studies, and researchers have revealed a number of mechani

FAQs

Why is chemoresistance a major problem in gastric cancer treatment?

Chemoresistance prevents patients from receiving sustained benefit from chemotherapy, leading to tumor recurrence, metastasis, and death.

How can chemoresistance in gastric cancer cells be classified?

It can be divided into primary drug resistance and acquired drug resistance, with acquired resistance arising after long-term or repeated exposure to chemotherapeutic drugs.

What is the role of drug efflux mediated by membrane proteins in chemoresistance?

Abnormally high expression of drug-resistance-related membrane proteins can pump chemotherapeutic drugs out of cancer cells or sequester them in membranous organelles, lowering intracellular drug concentration or altering drug distribution.

Sep 21, 2026

Uploaded by Asher