Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinoma.
BACKGROUND
Oesophageal adenocarcinoma is an increasingly common cancer with a poor prognosis. It develops in a stepwise progression from Barrett's metaplasia to dysplasia, and then adenocarcinoma followed by metastasis.


OBJECTIVE
To outline the key molecular changes in oesophageal adenocarcinoma and to summarize the chemopreventative and therapeutic strategies proposed.


METHODS
A literature search was performed to identify appropriate research papers in the field. Search terms included: Barrett's (o)esophagus, intestinal metaplasia, (o)esophageal adenocarcinoma, molecular changes, genetic changes, pathogenesis, chemoprevention, therapeutic strategies and treatment. The search was restricted to English language articles.


RESULTS
A large number of molecular changes have been identified in the progression from Barrett's oesophagus to oesophageal adenocarcinoma although there does not appear to be an obligate order of events. Potential chemoprevention strategies include acid suppression, anti-inflammatory agents and antioxidants. In established adenocarcinoma, targeted treatments under evaluation include receptor tyrosine kinase inhibitors of EGFR and cyclin-dependent kinase inhibitors, which may benefit a subgroup of patients.


CONCLUSIONS
Advances in molecular methodology have led to a greater understanding of the oesophageal adenocarcinoma pathways, which provides opportunities for chemoprevention and therapeutic strategies with a mechanistic basis. More work is required to assess both the safety and efficacy of these new treatments.
Peters
C J
CJ
MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrookes Hospital, Hills Road, Cambridge, UK.
Fitzgerald
R C
RC
D000230:Adenocarcinoma / Q000209:etiology / Q000517:prevention & control*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D049109:Cell Proliferation; D018890:Chemoprevention / Q000379:methods; D018450:Disease Progression; D004383:Duodenogastric Reflux / Q000517:prevention & control; D004938:Esophageal Neoplasms / Q000209:etiology / Q000517:prevention & control*; D018815:Genes, erbB; D006801:Humans
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants