Predictive Biomarkers In Metastatic Gastroesophageal Cancer Patients

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Background

Since the seminal papers by the Cancer Genome Atlas and Asian Cancer Research Group characterizing the molecular landscape of gastric cancers, it has been difficult to translate these findings into clinical practice. Although several validated and recurrently altered molecular targets are known, early attempts with matched therapies have been disappointing. With the increasing use of clinical next-generation sequencing (NGS) tests and circulating tumor DNA (ctDNA), there is a growing body of literature relating clinical and molecular features with a response to targeted agents and immunotherapies.

A common theme that has emerged within molecular biomarkers is the problem of pre-existing subclonal populations lacking a given biomarker and acquired intra- and inter-tumoral heterogeneity under therapeutic pressures. Selection based on single protein expression fails to capture underlying gastroesophageal cancer heterogeneity and underlies the disappointing clinical data seen in some targeted therapy trials. Early clinical data with baseline and serial molecular assessments is starting to allow patient stratification by composite molecular markers, thus optimizing selection for targeted and immune-based approaches. In this Research Topic, we will examine the data supporting expanded biomarker testing, predictive biomarkers, and emerging approaches to address heterogeneity in gastroesophageal cancers. Authors are welcome to submit Original Research, Review, Perspective articles as well as Case Reports focused on but not limited to:

1) Clinical and molecular predictors of response and/or resistance to targeted therapies in gastroesophageal cancers.
2) Clinical and molecular predictors of response and/or resistance to immune therapies in gastroesophageal cancers.
3) Pilot clinical data supporting targeted therapy activity in molecularly defined subgroups.
4) The clinical implications and utility of ctDNA in gastroesophageal cancers.
5) The role of single-cell -omics to inform treatment outcome with targeted agents.
6) Efforts to address key unanswered questions in gastroesophageal cancers.
7) Adaptive clinical trial designs to address heterogeneity in gastroesophageal cancers.

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