Abstract
Cancer of the esophagus is an aggressive disease with early lymphatic and hematogenous dissemination and at present often considered as one clinical entity because of their comparable increasing incidence, prognosis and optimal treatment options. However, it is still a matter of debate whether these malignancies have the same pathogenesis and genotype. Despite recent advances, treatment of upper gastrointestinal malignancies remains a significant challenge. Molecular pathology has revealed many molecular mechanisms of disease progression, which are related to prognosis. Better knowledge of molecular bases may lead to new paradigms, improved prognostication, early diagnosis and individually tailored therapeutic options. This review summarizes the rationale, preclinical evidence, retrospective clinical analyses and the interim clinical data pertaining HER2 therapy and many other molecular pathways.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
• In the Western world, there has been an alarming rise in the incidence and prevalence of adenocarcinoma during recent decades.
• Cancer of the esophagus shows multiple genetic alterations, which indicate that progression of cancer is a multistep complex process with many different alterations.
• Targeted molecular therapy in upper gastrointestinal cancer has become an increasingly popular topic over the past few years.
• A bewildering number of biomarkers have been described. Many genes and molecules have prognostic impact (EGFR, Her-2/Neu, survivin, estrogen, Cox-2, E-cadherin, OCT4, SOX2, IGF-1 and CRP).
• Better knowledge of molecular bases may lead to new paradigms, improved prognostication, early diagnosis and individually tailored therapeutic options.
• Drug development has already been transformed with the identification and ability to direct treatment at specific molecular targets (e.g., COX-2, HER2, VEGF and tyrosine kinase inhibitors).
• It is likely that therapeutic intervention at the level of genes and molecules with great prognostic power and its signaling pathways will have the largest impact on long-term survival.
• In future, gene expression analysis with microarrays may reveal important prognostic information and the discovery of new genes and molecules associated with tumor progression and dissemination will enhance prognostication and offers adjuvant therapeutic options.