Current Landscape of Molecular Biomarkers in Gastroesophageal Tumors and Potential Strategies for Co-Expression Patterns

Abstract

The treatment of metastasized gastroesophageal adenocarcinoma largely depends on molecular profiling based on immunohistochemical procedures. Therefore, the examination of HER2, PD-L1, and dMMR/MSI is recommended by the majority of clinical practice guidelines, as positive expression leads to different treatment approaches. Data from large phase-III trials and consequent approvals in various countries enable physicians to offer their patients several therapy options including immunotherapy, targeted therapy, or both combined with chemotherapy. The introduction of novel therapeutic targets such as CLDN18.2 leads to a more complex decision-making process as a significant number of patients show positive results for the co-expression of other biomarkers besides CLDN18.2. The aim of this review is to summarize the current biomarker landscape of patients with metastatic gastroesophageal tumors, its direct clinical impact on daily decision-making, and to evaluate current findings on biomarker co-expression. Furthermore, possible treatment strategies with multiple biomarker expression are discussed.

Keywords: CLDN18.2; DKK-1; HER-2; PD-L1; TIGIT; esophageal cancer; gastric cancer; gastroesophageal tumors; microsatellite instability; molecular biomarkers.

Figure 1

Comparison of the TAP to TPS and CPS. The visual estimation of tumor area positivity is less time consuming than counting each cell. CPS = combined positive score; IC = immune cell; n, number; PD-L1 = programmed death-ligand 1; TAP = tumor area positivity; TC = tumor cell; TPS = tumor proportion score.

Figure 2

During the process of carcinogenesis, the loss of cellular polarity leads to aberrant Claudin 18.2 expression, which is associated with irregular proliferation and invasion.