Progress and challenges in gastroesophageal cancer

Gastroesophageal adenocarcinoma (GEA) is a challenging disease; most GEA patients do not live for more than a year after a diagnosis of advanced disease. Development of effective tar geted therapeutics for GEA patients lags behind other cancers. Progress in molecular biology has provided subclassifications of gastroesophageal cancer which may have prognostic and predictive utility and has identified novel therapeutic targets. Heterogeneity in biomarker expression has been a challenge in new drug development, leading to negative trials of targeted therapeutics in the first and second line setting. In this review, we discuss developments in understanding GEA biology, focus on putative prognostic and predictive biomarkers and examine the results of important recent clinical trials. The role of hetergeneity in GEA outcomes is reviewed and we discuss intraand interpatient heterogenetiy in the context of emergent data on liquid biopsy and how this might complement tissue diagnosis and determine treatment in the GEA field. Finally, we examine recent results from international trials using immune checkpoint blockade with anti-PD-1, anti-CTLA4, and anti-PD-L1 antibodies, in an effort to dissect the interaction between gastroesophageal tumour and enviroment on the immune response and we reflect on how immune checkpoint blockade may impact of treatment paradigms for GEA in future. (c) 2020 Elsevier Inc. All rights reserved.