Advancements in Gastric Cancer Detection and Treatment

Introduction to Gastric Cancer and Its Global Impact

Gastric cancer (GC) is a significant global health challenge, ranking fifth in incidence and third in cancer-related mortality worldwide (Bray et al., 2024). The high prevalence of gastric cancer, with more than one million new cases diagnosed annually, is largely attributed to a combination of genetic, environmental, and lifestyle factors. The prognosis for patients diagnosed with advanced stages of gastric cancer remains dismal, with a five-year survival rate of less than 30% (Shen et al., 2024). The asymptomatic nature of early gastric cancer leads to late-stage diagnosis in over 80% of patients, highlighting the urgent need for improved screening methods (Katai et al., 2018).

The disease’s pathogenesis is complex, with chronic infection by Helicobacter pylori (H. pylori) recognized as a major risk factor (Wang et al., 2015). This bacterium triggers inflammatory responses and promotes dysplastic changes in gastric epithelium, contributing to gastric carcinogenesis (Fang et al., 2023). Understanding the molecular mechanisms involved in gastric cancer development is pivotal for developing novel diagnostic and therapeutic strategies.

Importance of Early Detection and Screening Methods

Early detection of gastric cancer is crucial for improving patient outcomes. Traditional diagnostic methods, such as endoscopy and biopsy, although effective, are invasive and often associated with patient discomfort, leading to low compliance rates (Zhang et al., 2024). Additionally, these methods depend heavily on the skill and experience of the endoscopist, which can lead to variability in diagnostic accuracy (Hong et al., 2024).

Recent advancements in non-invasive diagnostic techniques are promising for enhancing early detection rates. For instance, liquid biopsy methods that examine circulating tumor cells (CTCs) and tumor-associated biomarkers are gaining traction. These methods could provide a less invasive alternative to conventional endoscopy while maintaining diagnostic efficacy (Chen et al., 2024). The development of novel biomarkers such as hexokinase 2 (HK2) in gastric lavage fluid shows a potential pathway to identify malignancies early (Qian et al., 2025).

Role of Hexokinase 2 in Identifying Tumor Cells

Hexokinase 2 (HK2) is an enzyme that plays a critical role in the metabolic reprogramming of cancer cells, facilitating the Warburg effect, wherein cancer cells preferentially utilize glycolysis for energy production even in the presence of oxygen (Chen et al., 2024). This metabolic shift not only supports rapid cell proliferation but also provides a potential biomarker for identifying malignant cells.

In a recent study, the HK2 assay demonstrated an 80% sensitivity and 96% specificity in detecting early-stage gastric cancer from gastric lavage samples (Qian et al., 2025). The assay identifies exfoliated tumor cells based on their glycolytic activity, representing a significant advancement in non-invasive cancer diagnostics. This method could potentially revolutionize the approach to gastric cancer screening, moving towards a more patient-friendly model.

Benefits of Single-Cell Sequencing in Cancer Diagnosis

Single-cell sequencing (SCS) represents a transformative technology that enables the comprehensive analysis of the genomic and transcriptomic landscapes of individual cells (Zhang et al., 2024). In the context of gastric cancer, SCS allows for the identification of copy number variations (CNVs) that are hallmarks of malignancy. This capability was highlighted in a study where HK2-positive cells retrieved from gastric lavage were subjected to SCS, revealing CNV profiles that confirmed their neoplastic nature (Qian et al., 2025).

The integration of SCS with traditional diagnostic methods enhances the accuracy of cancer detection and provides insights into tumor heterogeneity, which can inform personalized treatment strategies. By understanding the specific genomic alterations within tumor cells, clinicians can tailor therapeutic approaches that specifically target these abnormalities, potentially increasing treatment efficacy and reducing adverse effects.

Innovative Approaches for Non-Invasive Gastric Cancer Screening

Recent innovations in non-invasive screening methods for gastric cancer include the development of assays that analyze gastric lavage fluid for tumor markers. These methods are based on the detection of metabolic changes associated with cancer cells, such as increased HK2 expression. The use of gastric lavage for early detection presents a viable alternative to invasive endoscopic procedures, potentially increasing patient compliance and early diagnosis rates (Chen et al., 2024).

Furthermore, the combination of HK2 assays with SCS techniques can enhance diagnostic sensitivity, allowing for the identification of malignant cells even at precancerous stages. This dual approach not only facilitates earlier detection but also provides critical information on the molecular characteristics of the disease, guiding treatment decisions.

Future Directions in Gastric Cancer Research and Management

The landscape of gastric cancer research is rapidly evolving, with ongoing studies focusing on novel biomarkers, improved diagnostic methods, and targeted therapies. Future research should prioritize the exploration of additional metabolic markers that can complement HK2 in detecting gastric cancer and monitor the progression of precancerous lesions.

Moreover, the integration of artificial intelligence (AI) and machine learning models in analyzing complex datasets from SCS and liquid biopsies could further enhance the precision of gastric cancer diagnostics. AI algorithms could identify patterns that may not be evident through traditional analysis, leading to earlier and more accurate diagnosis of gastric cancer.

In parallel, therapeutic strategies targeting the metabolic pathways associated with gastric cancer, including inhibitors of glycolysis or pathways regulated by HK2, are promising avenues for research. These strategies could potentially lead to the development of novel pharmacological interventions that improve outcomes for patients diagnosed with gastric cancer.

FAQ Section

What is gastric cancer?

Gastric cancer, also known as stomach cancer, is a type of cancer that begins in the stomach lining. It ranks as one of the most common cancers worldwide and is associated with high mortality rates.

How is gastric cancer diagnosed?

Gastric cancer is typically diagnosed through endoscopy and biopsy. However, newer non-invasive methods, such as the HK2 assay on gastric lavage fluid, are being developed to improve early detection rates.

What is hexokinase 2?

Hexokinase 2 (HK2) is an enzyme involved in glucose metabolism, particularly in cancer cells that favor glycolysis for energy production. It serves as a potential biomarker for identifying malignant cells.

What role does single-cell sequencing play in cancer diagnosis?

Single-cell sequencing allows for the detailed analysis of the genomic characteristics of individual tumor cells, providing insights into tumor heterogeneity and facilitating the identification of malignancy through copy number variation analysis.

What are the innovative screening methods for gastric cancer?

Innovative screening methods include non-invasive assays that analyze gastric lavage fluid for metabolic markers such as HK2, and the use of single-cell sequencing to confirm malignancy and provide insights into the tumor’s genomic landscape.

References

1. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., & Soerjomataram, I. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 74(3), 229-263

2. Katai, H., Ishikawa, T., Akazawa, K., et al. (2018). Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001-2007). Gastric Cancer, 21(1), 144-154

3. Shen, L., Shan, Y.-S., Hu, H.-M., et al. (2024). Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol, 14(12), e535-e547 13)70436-4

4. Qian, P., Sun, J., Zhao, Z., & Lu, P. (2025). Early Detection of Malignant Cells in Gastric Lavage via Hexokinase 2 and Single-Cell Sequencing for Gastric Cancer Diagnosis. Risk Manag Healthc Policy, 18, 1231-1240. https://doi.org/10.2147/RMHP.S510123

5. Chen, Y., Wu, Y., Wang, J., et al. (2024). The role of hexokinase 2 in identifying tumor cells in gastric cancer. Clin Pharmacokinet. https://doi.org/10.1007/s40262-024-01466-0

6. Zhang, Z., Liu, M., Li, S., Jiang, C. (2024). Endoscopic resection compared with gastrectomy to treat early gastric cancer: a systematic review and meta-analysis. PLoS One, 10(12), e0144774. https://doi.org/10.1371/journal.pone.0144774