Deciphering drug resistance in gastric cancer: Potential mechanisms and future perspectives
Jiahua Liu1, Qihang Yuan1, Hui Guo1
1First Affiliated Hospital of Dalian Medical University, Dalian, China.
Abstract:
Gastric cancer (GC) is a malignant tumor that originates from the epithelium of the gastric mucosa. The latest global cancer statistics show that GC ranks fifth in incidence and fourth in mortality among all cancers, posing a serious threat to public health. While early-stage GC is primarily treated through surgery, chemotherapy is the frontline option for advanced cases. Currently, commonly used chemotherapy regimens include FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine). However, with the widespread use of chemotherapy, an increasing number of cases of drug resistance have emerged. This article primarily explores the potential mechanisms of chemotherapy resistance in GC patients from five perspectives: cell death, tumor microenvironment, non-coding RNA, epigenetics, and epithelial-mesenchymal transition. Additionally, it proposes feasibility strategies to overcome drug resistance from four angles: cancer stem cells, tumor microenvironment, natural products, and combined therapy. The hope is that this article will provide guidance for researchers in the field and bring hope to more GC patients.
Insights
Gastric cancer chemotherapy resistance is a growing problem. This review explores resistance mechanisms and strategies to overcome them, offering hope for advanced gastric cancer patients.
Area of Science:
- Oncology
- Cancer Research
- Gastroenterology
Background:
- Gastric cancer (GC) is a leading cause of cancer incidence and mortality worldwide.
- Chemotherapy, including FOLFOX and XELOX, is a primary treatment for advanced GC.
- Emerging drug resistance significantly limits the efficacy of current chemotherapy regimens.
Purpose of the Study:
- To explore the multifaceted mechanisms underlying chemotherapy resistance in gastric cancer.
- To propose viable strategies for overcoming drug resistance in GC patients.
Main Methods:
- Review of potential resistance mechanisms including cell death, tumor microenvironment, non-coding RNA, epigenetics, and epithelial-mesenchymal transition.
- Analysis of strategies to overcome resistance, focusing on cancer stem cells, tumor microenvironment modulation, natural products, and combination therapies.
Main Results:
- Chemotherapy resistance in GC is complex, involving intricate biological pathways.
- Multiple avenues exist for overcoming resistance, including targeting cancer stem cells and modulating the tumor microenvironment.
Conclusions:
- Understanding resistance mechanisms is crucial for developing effective therapeutic strategies.
- Targeted interventions and combination therapies hold promise for improving outcomes in advanced gastric cancer.
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