Stomach Cancer
Stomach cancer, also known as gastric cancer, is a malignant neoplasm arising from the lining of the stomach. The disease typically develops through a multistep process involving chronic inflammation, atrophic gastritis, intestinal metaplasia, dysplasia, and eventual transformation into carcinoma. The pathogenesis of stomach cancer is multifactorial, with risk factors including Helicobacter pylori infection, dietary influences (such as high salt intake and consumption of smoked or preserved foods), genetic predisposition, smoking, and certain hereditary cancer syndromes. Molecular alterations such as mutations in CDH1, TP53, and other oncogenes and tumor suppressor genes play a role in tumorigenesis. Stomach cancer exerts significant health impacts, as it is often diagnosed at an advanced stage due to nonspecific symptoms like dyspepsia, weight loss, anorexia, and abdominal pain. Advanced disease may lead to obstruction, bleeding, and metastatic complications, contributing to substantial morbidity and mortality.
Adenocarcinoma is the most prevalent type of stomach cancer, accounting for approximately 90-95% of all cases. It arises from the glandular epithelium of the gastric mucosa and is further classified into intestinal and diffuse subtypes based on histological features. The intestinal type tends to form gland-like structures and is often associated with chronic gastritis and environmental risk factors, while the diffuse type is characterized by poorly cohesive cells, including signet ring cells, and is more frequently linked to genetic mutations such as those in the CDH1 gene.
GISTs are rare mesenchymal tumors originating from the interstitial cells of Cajal in the stomach wall. They are characterized by mutations in the KIT or PDGFRA genes and typically present as submucosal masses. GISTs may be asymptomatic or cause symptoms related to bleeding or obstruction, and their biological behavior ranges from benign to highly malignant.
Primary gastric lymphoma represents a small percentage of stomach cancers and arises from lymphoid tissue within the stomach, most commonly as mucosa-associated lymphoid tissue (MALT) lymphoma. These tumors are frequently associated with chronic H. pylori infection and may respond to eradication therapy in early stages.
Gastric carcinoid tumors are neuroendocrine neoplasms that arise from enterochromaffin-like cells in the stomach. They are relatively rare and may be associated with chronic atrophic gastritis, hypergastrinemia, or genetic syndromes such as multiple endocrine neoplasia type 1. Carcinoid tumors are generally indolent but can occasionally behave aggressively.
Squamous cell carcinoma of the stomach is exceedingly rare and arises from squamous metaplasia of the gastric mucosa. It is distinguished histologically by the presence of keratinizing squamous cells and lacks glandular differentiation.
Stomach cancer is a major global health concern, ranking as the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. According to GLOBOCAN 2020 estimates, there were over one million new cases and approximately 769,000 deaths attributable to gastric cancer annually. The incidence varies geographically, with the highest rates observed in East Asia (particularly Japan, Korea, and China), Eastern Europe, and parts of South America. Incidence and mortality rates have declined in many regions due to improved food preservation, decreased prevalence of H. pylori infection, and dietary changes. Stomach cancer is more common in men than women, with a male-to-female ratio of approximately 2:1, and the median age at diagnosis is typically between 60 and 70 years. The five-year survival rate remains low, particularly in advanced stages, and prognosis is highly dependent on the stage at diagnosis, histological subtype, and molecular characteristics.
The diagnosis of stomach cancer is based on a combination of clinical evaluation, endoscopic visualization, histopathological assessment, and imaging studies. Initial evaluation typically involves upper gastrointestinal endoscopy, which allows direct visualization of the gastric mucosa and targeted biopsy of suspicious lesions. Histological examination of biopsy specimens confirms the diagnosis and provides information on tumor type and grade. Endoscopic ultrasound (EUS) is employed to assess the depth of tumor invasion and regional lymph node involvement. Cross-sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is essential for staging, detecting distant metastases, and guiding therapeutic planning. Positron emission tomography (PET) may be used in selected cases for further staging. Laboratory tests, including complete blood count, liver function tests, and tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), can provide additional information but are not specific for diagnosis. Staging is performed according to the TNM classification system, which evaluates tumor depth (T), nodal involvement (N), and distant metastasis (M). Accurate staging is critical for determining prognosis and selecting appropriate treatment strategies.
Claudiximab, also known as zolbetuximab or zolbetuximab-clzb, is a monoclonal antibody that targets Claudin 18.2 and is utilized in the treatment of certain gastric cancers expressing this protein. Cadonilimab is a bispecific antibody designed to modulate immune checkpoint pathways and enhance antitumor immunity in patients with stomach cancer. Disitamab vedotin is an antibody-drug conjugate directed against HER2, delivering cytotoxic agents selectively to HER2-expressing gastric tumors. Trastuzumab, including its variants trastuzumab-strf, trastuzumab-qyyp, and trastuzumab-dttb, is a monoclonal antibody that binds to the HER2 receptor and is indicated for the treatment of HER2-positive gastric cancer, often in combination with chemotherapy. Fam-trastuzumab deruxtecan, also referred to as trastuzumab deruxtecan or fam-trastuzumab deruxtecan-nxki, is an antibody-drug conjugate that combines trastuzumab with a topoisomerase I inhibitor, providing targeted cytotoxicity to HER2-expressing gastric cancer cells. Tislelizumab, or tislelizumab-jsgr, is a programmed death-1 (PD-1) inhibitor that enhances immune-mediated antitumor responses and is used in the management of advanced or metastatic gastric cancer.
| Structure | Generic Name | CAS Registry Number | Molecular Formula |
|---|---|---|---|
| claudiximab; zolbetuximab (Rec INN; USAN); zolbetuximab-clzb | 1496553-00-4 | ||
| cadonilimab (Rec INN; USAN) | 2233593-44-5 | ||
 | disitamab vedotin (Rec INN; USAN) | 2136633-23-1 | C68 H106 N11 O15 R S |
| trastuzumab; trastuzumab-strf | |||
 | [fam-]trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki; trastuzumab deruxtecan (Rec INN; USAN) | 1826843-81-5 | C52 H57 F N9 O13 R S |
| tislelizumab (Rec INN; USAN); tislelizumab-jsgr | 1858168-59-8 | ||
| trastuzumab; trastuzumab-qyyp | |||
| trastuzumab | |||
| trastuzumab; trastuzumab-dttb |
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Stomach Cancer
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