Esophageal Cancer
Esophageal cancer is a malignant neoplasm arising from the epithelial cells lining the esophagus, the muscular tube that conveys food from the pharynx to the stomach. The pathogenesis of esophageal cancer involves a multifactorial process including chronic irritation, inflammation, and genetic mutations that drive the transformation of normal esophageal mucosa into dysplastic and ultimately malignant cells. Key risk factors include tobacco use, excessive alcohol consumption, chronic gastroesophageal reflux disease (GERD), Barrett's esophagus, dietary nitrosamines, and certain infections such as human papillomavirus (HPV). The disease is characterized by local invasion, early lymphatic spread, and a propensity for distant metastasis, leading to significant morbidity and mortality. Health impacts are profound, as esophageal cancer often presents at an advanced stage, resulting in dysphagia, malnutrition, and a diminished quality of life, with overall survival rates remaining low despite advances in treatment.
Esophageal squamous cell carcinoma (ESCC) arises from the squamous epithelium that lines the upper and middle portions of the esophagus. This type is strongly associated with risk factors such as tobacco smoking, alcohol consumption, and dietary deficiencies. ESCC tends to develop through a sequence of chronic inflammation, squamous dysplasia, and carcinoma in situ, ultimately progressing to invasive cancer. It is the predominant histological subtype in many regions of Asia and Africa and is often linked to environmental and lifestyle exposures.
Esophageal adenocarcinoma (EAC) originates from glandular cells, typically in the lower third of the esophagus, often in the context of Barrett's esophagus, a metaplastic change resulting from chronic gastroesophageal reflux disease (GERD). EAC has become the most common subtype in Western countries, particularly among white males. The progression from Barrett's esophagus to dysplasia and then to adenocarcinoma is well-characterized, and risk factors include obesity, smoking, and chronic reflux. EAC is notable for its aggressive behavior and rapid progression.
Other rare histological types of esophageal cancer include small cell carcinoma, sarcomas, lymphomas, and melanomas. These subtypes are uncommon and may present with distinct biological behaviors and treatment responses. Their management often requires specialized, multidisciplinary approaches.
Esophageal cancer is the eighth most common cancer worldwide and ranks sixth in cancer-related mortality. Globally, there are approximately 604,000 new cases and 544,000 deaths annually, reflecting the aggressive nature of the disease and its typically late presentation. The incidence and histological distribution vary geographically: esophageal squamous cell carcinoma predominates in high-incidence regions such as East Asia, parts of Africa, and South America, while esophageal adenocarcinoma is more prevalent in North America, Western Europe, and Australia. Males are affected more frequently than females, with a male-to-female ratio ranging from 3:1 to 7:1, depending on the region and subtype. The disease predominantly affects individuals over the age of 60, and survival rates remain poor, with 5-year survival typically less than 20% in most settings.
The diagnosis of esophageal cancer involves a combination of clinical evaluation, endoscopic assessment, histopathological confirmation, and staging investigations. Patients frequently present with progressive dysphagia, odynophagia, weight loss, or upper gastrointestinal bleeding. Esophagogastroduodenoscopy (EGD) is the primary diagnostic modality, enabling direct visualization of the tumor, tissue biopsy, and assessment of the extent of local invasion. Histopathological analysis of biopsy specimens confirms the diagnosis and determines the cancer subtype. Endoscopic ultrasound (EUS) is critical for evaluating the depth of tumor invasion and regional lymph node involvement. Cross-sectional imaging, including computed tomography (CT) and positron emission tomography (PET), is employed for staging, detecting distant metastases, and guiding therapeutic decisions. Additional workup may include bronchoscopy for tumors in the upper esophagus and molecular profiling in select cases. The diagnosis is ultimately based on the integration of clinical, endoscopic, pathological, and radiological findings, following established criteria such as the TNM staging system.
Several therapeutic agents have been developed and utilized in the management of esophageal cancer, targeting various aspects of tumor biology and the immune response. Serplulimab is a monoclonal antibody that inhibits programmed cell death protein 1 (PD-1), thereby enhancing antitumor immune activity. Sugemalimab is another monoclonal antibody targeting programmed death-ligand 1 (PD-L1), used to modulate immune responses against malignant cells. Tislelizumab, a PD-1 inhibitor, is employed for its immune checkpoint blockade properties, facilitating the activation of cytotoxic T lymphocytes against tumor cells. Sintilimab is also a PD-1 inhibitor, contributing to immune-mediated tumor cell destruction. Toripalimab, another anti-PD-1 monoclonal antibody, is used to potentiate immune responses in patients with esophageal malignancies. Lambrolizumab, known as pembrolizumab, targets PD-1 and is indicated for the treatment of patients with advanced or metastatic esophageal cancer, particularly in those with specific biomarker profiles. Nivolumab, a PD-1 immune checkpoint inhibitor, is approved for use in advanced esophageal cancer, offering improved survival outcomes in certain patient populations. Ipilimumab functions as a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, acting to promote T-cell mediated antitumor activity and is used in combination with other immunotherapies. Talaporfin sodium, a photosensitizer, is applied in photodynamic therapy for the local treatment of superficial esophageal tumors, offering a non-surgical option for select patients. Docetaxel, a cytotoxic taxane chemotherapeutic agent, disrupts microtubule function and is utilized as part of combination chemotherapy regimens for advanced or metastatic esophageal cancer, contributing to tumor reduction and disease control.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| serplulimab (Rec INN; USAN) | 2231029-82-4 | |||
| sugemalimab (Rec INN) | 2256084-03-2 | |||
| tislelizumab (Rec INN; USAN); tislelizumab-jsgr | 1858168-59-8 | |||
| sintilimab (Rec INN; USAN) | 2072873-06-2 | |||
| toripalimab (Rec INN; USAN) | 1924598-82-2 | |||
| lambrolizumab; pembrolizumab (Rec INN; USAN) | 1374853-91-4 | |||
| nivolumab (Rec INN; USAN) | 946414-94-4 | |||
| ipilimumab (Rec INN; USAN) | 477202-00-9 | |||
 | mono-L-aspartyl chlorin e6; talaporfin sodium (Rec INNM; USAN) | 220201-34-3 | C38 H37 N5 O9 . 4 Na | 799.688 |
 | docetaxel (Rec INN; USAN; BAN); docetaxol | 114977-28-5 | C43 H53 N O14 | 807.879 |
Make Order
Experimental Scheme
Implementation
Conclusion
Esophageal Cancer
Alfa Cytology, a preclinical research solution provider, provides its clients with one-stop solutions to accelerate cancer therapeutics discovery and development.