Strategies for molecular intervention in esophageal cancers and their precursor lesions.

Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Diseases of the Esophagus (Impact Factor: 2.06). 02/1999; 12(3):181-5. DOI: 10.1046/j.1442-2050.1999.00044.x
Source: PubMed

ABSTRACT Molecular analysis of malignant transformation in Barrett's epithelium provides insight into the temporal nature and significance of individual genetic events during multistep esophageal carcinogenesis. Potential targets for intervention in esophageal neoplasms include mutations involving retinoblastoma (Rb) and p53 tumor-suppressor pathways as well as tyrosine kinase cascades, which are known to promote cell cycle progression. Data from recent experiments provide the preclinical rationale for novel pharmacologic interventions in established esophageal cancers, and suggest strategies for chemoprevention in patients at risk for the development of these neoplasms.

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    ABSTRACT: Yu-Xiao Yang – University of Pennsylvania, Philadelphia, USA
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    ABSTRACT: Barrett's esophagus is characterised by the presence of specialised intestinal metaplasia in the lower esophagus. Its importance is related primarily to its link with adenocarcinoma of the lower esophagus, often preceded by dysplastic changes. The incidence of this carcinoma has increased dramatically over the last few decades. Although modern treatments, particularly acid suppression with proton pump inhibitors, have been most useful in controlling the reflux symptoms associated with Barrett's esophagus, they have not reduced the incidence of adenocarcinoma of the esophagus. The same can be said about anti-reflux surgery. Surgical excision of Barrett's esophagus has been advocated when high-grade dysplasia is detected; this carries considerable morbidity and mortality, so alternative treatments are being developed. This update summarises recent information concerning newer treatments aimed at eradicating Barrett's esophagus. These vary from thermal coagulation (using electrocoagulation and heater probes) to lasers, photodynamic therapy and mechanical methods. Of these, photodynamic therapy using a porphyrin precursor (5-amino-laevulinic acid) seems to give the most consistent satisfactory results with a minimum of complications. However, persistence of some metaplastic cells beneath the neo-squamous layer remains a problem. Ongoing effective acid control (by medical or surgical therapy) is also essential to prevent recurrence of Barrett's esophagus. Future research is aimed at perfecting these methods. Ultimately, it may be possible to understand the molecular biology which could help to predict which patients are at greatest risk of developing dysplastic and carcinomatous changes.
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