Understanding Gastric Cancer: Mechanisms and Modern Treatment Approaches

What is gastric cancer?

Gastric cancer, also referred to as stomach cancer, is a malignant disease characterized by uncontrolled cell growth originating in the gastric mucosa. The stomach is located in the upper central abdomen, beneath the rib cage, and plays a critical role in food digestion through mechanical processing and acid secretion.

Gastric cancer can arise in any anatomical region of the stomach. Globally, most tumors develop in the body of the stomach, while in Western countries, including the United States, cancers more frequently originate near the gastroesophageal junction, the area where the esophagus meets the stomach. Tumor location is a key determinant in staging, treatment planning, and prognosis.

Early-stage gastric cancer confined to the stomach wall is potentially curable. However, most cases are diagnosed at advanced stages, when the disease has invaded deeper layers of the stomach or spread to distant organs, making treatment more complex and outcomes less favorable.

Clinical manifestations of gastric cancer

Early gastric cancer often develops silently, without specific symptoms. When present, initial manifestations tend to be nonspecific and may resemble common digestive disorders.

Common symptoms include:

• Difficulty swallowing

• Persistent upper abdominal pain or discomfort

• Early satiety, feeling full after small meals

• Postprandial bloating

• Loss of appetite

• Heartburn or indigestion

• Nausea or vomiting

• Unintentional weight loss

• Fatigue and weakness

• Black, tarry stools indicating gastrointestinal bleeding

In advanced disease, symptoms may reflect systemic involvement or metastasis. Spread to lymph nodes may cause palpable masses. Liver involvement can lead to jaundice. Peritoneal dissemination may result in abdominal fluid accumulation and visible distension.

Pathophysiology and causes

The precise cause of gastric cancer remains incompletely understood. Current evidence suggests that the disease develops through a multistep process initiated by chronic injury to the gastric lining. Repeated mucosal damage promotes genetic alterations in epithelial cells, affecting DNA sequences responsible for cell growth, apoptosis, and repair.

These mutations cause abnormal cell proliferation, resistance to programmed cell death, and eventual tumor formation. As malignant cells invade deeper layers of the stomach wall, they gain the ability to enter lymphatic and blood vessels, enabling metastatic spread.

Factors that may initiate or accelerate this process include:

• Chronic gastric inflammation

• Long-standing acid reflux

• High dietary salt intake

• Persistent infection of the gastric mucosa

Not all individuals exposed to these factors develop cancer, indicating a complex interaction between environmental exposure, genetic susceptibility, and host immune response.

Histological types of gastric cancer

Gastric cancer is classified based on the cell type of origin:

• Adenocarcinoma
  The most common form, arising from mucus-producing glandular cells. It accounts for the vast majority of gastric malignancies.

• Gastrointestinal stromal tumors (GIST)
  Rare tumors originating from specialized interstitial cells within the stomach wall.

• Neuroendocrine (carcinoid) tumors
  Arise from hormone-producing neuroendocrine cells and vary widely in aggressiveness.

• Gastric lymphoma
  Develops from immune cells within gastric lymphoid tissue, often associated with chronic immune stimulation.

Risk factors

Several conditions increase the likelihood of developing gastric cancer:

• Chronic gastroesophageal reflux

• Diet rich in salted, smoked, or preserved foods

• Low intake of fruits and vegetables

• Chronic infection of the stomach lining

• Long-standing gastritis

• Tobacco use

• Gastric polyps

• Family history of gastric cancer

• Inherited cancer syndromes affecting DNA repair or cell growth regulation

Genetic syndromes associated with increased risk include hereditary diffuse gastric cancer, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis, and familial adenomatous polyposis.

Diagnostic evaluation

Diagnosis is based on a combination of clinical suspicion, endoscopic examination, histological confirmation, and imaging studies. Upper gastrointestinal endoscopy allows direct visualization of the gastric mucosa and biopsy of suspicious lesions. Imaging modalities are used to assess local invasion and distant spread.

Accurate staging is essential for determining prognosis and selecting appropriate therapy.

Therapeutic strategies

Treatment depends on tumor location, histological type, stage, and patient health status. Surgery remains the cornerstone of curative treatment when the disease is localized. In advanced stages, therapy may include systemic treatments administered before or after surgery to improve outcomes.

Multimodal approaches are frequently required, integrating surgical, medical, and supportive care to manage symptoms and improve quality of life.

Prevention and risk reduction

Although gastric cancer cannot always be prevented, risk can be reduced through lifestyle and dietary measures:

• Increasing consumption of fruits and vegetables

• Reducing intake of salted and smoked foods

• Avoiding tobacco use

• Addressing chronic gastric conditions

• Identifying high-risk individuals through family history assessment and surveillance when appropriate

Early detection significantly improves prognosis, particularly in populations with increased risk.

Scientific references

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2. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022. NCCN Clinical Practice Guidelines in Oncology.

3. Correa P. A human model of gastric carcinogenesis. Cancer Research. 1988;48(13):3554–3560.

4. Crew KD, Neugut AI. Epidemiology of gastric cancer. World Journal of Gastroenterology. 2006;12(3):354–362.

5. Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. The Lancet. 2016;388(10060):2654–2664.