Molecular Basis of Esophageal Cancer Development and Progression
Introduction
This article is divided into 2 separate, but parallel, sections regarding the molecular mechanisms underlying the development and progression of esophageal neoplasms. Adenocarcinomas and squamous cell carcinomas are known to have differing risk factors and characteristic demographic factors, suggesting that the molecular events that lead to each of these cancers are distinct. In addition, our developing understanding of the molecular biology of these diseases confirms this assumption. Therefore, the first section of the article describes the current understanding of molecular events leading to esophageal adenocarcinomas and the second section relates to the development of esophageal squamous cell carcinomas.
Section snippets
Epidemiology
The overall epidemiology of esophageal cancers is more thoroughly described elsewhere in this issue by Reed and colleagues. The incidence of esophageal adenocarcinoma has increased by 400% over the past decade, which is greater than any other malignancy in the same period. This phenomenon has been observed primarily in Western nations, whereas squamous cell cancers remain the predominant histology in most of Asia and other nations.
The most notable risk factors for adenocarcinoma are
Summary
The most clinically relevant molecular targets in esophageal cancer are those targets previously identified in other more common types of carcinomas, and the importance of these proteins in esophageal cancer was later established. Previous clinical studies of targeted agents in the treatment of other cancers has established clinical safety profiles, which has facilitated the adoption of agents such as inhibitors of EFGR, Her2/neu, and VEGF for the treatment of esophageal cancer. Ongoing
Squamous cell carcinoma
Worldwide, squamous cell carcinoma of the esophagus is more common than adenocarcinoma. In America, squamous cell cancers comprise only 20% of all esophageal cancers, and this incidence is declining. Smoking and alcohol consumption are considered the major risk factors for the development of squamous cell cancers, and the molecular pathways leading from these environmental exposures to carcinogenesis are still being established. Both alcohol and smoking are known to have numerous carcinogenic
Summary
Our understanding of the molecular events responsible for the development of esophageal adenocarcinoma and squamous cell carcinoma continues to evolve. As further knowledge is gained, more options for targeted molecular therapy are anticipated. Currently, targeted agents in clinical trials are those agents previously investigated for the treatment of other diseases that are more prevalent in America. Early results from several nonrandomized trials that include these agents are encouraging, but
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Protein coding gene CRNKL1 as a potential prognostic biomarker in esophageal adenocarcinoma
2017, Artificial Intelligence in MedicineCitation Excerpt :A biological marker can afford an indication of the disease condition, whether normal or abnormal, which should be sensitive, specific and cost-effective. In current clinical practice, PTGS2, EGFR, ERBB2 and TP53 were considered as the optimal prognostic EAC biomarkers [7–11]. COX-2, an induced enzyme, is encoded by the PTGS2 gene, and its expression affects survival outcomes of patients in EAC [12,13].
FOXQ1 promotes esophageal cancer proliferation and metastasis by negatively modulating CDH1
2015, Biomedicine and PharmacotherapyCitation Excerpt :Due to difficulties in early diagnosis and poor efficacy of treatment of ESCC, the 5-year survival rate remains dismal [2], despite improvements having been made in treatments such as surgical resection and adjuvant chemoradiation. Epidemiological studies have suggested tobacco, alcohol, nitrosamines, physical injury and chronic inflammation as major risk factors in ESCC [3–6]. Previous studies manifested that tumor suppressor p53 and Rb frequently altered, including mutation of p53, loss of heterozygosity of Rb [4,7].
Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma
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