Does tumor profile in gastric and gastroesophageal (GE) junction cancer justify off-label use of targeted therapy?-a narrative review.

Despite significant therapeutic progress, gastric cancer remains among the most deadly forms of cancer encountered in clinical practice, and this remains true even in the context of declining incidence. Outcomes in advanced disease remain poor and therapy is rarely curative in this setting. As our understanding of tumor profile gains sophistication, a growing interest in targeted therapies and moreover the use of tumor profile to inform these therapies has developed in the hopes of altering nearly uniformly poor outcomes. A wide and growing array of molecular targets have been identified in the recent past. Targets of potential clinical interest include human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor (FGFR). This advanced molecular understanding has been increasingly used to justify the off-label usage of targeted therapies, though the efficacy of this approach warrants careful consideration. While targeted agents have demonstrated efficacy across a wide range of malignancies, even with molecular profiling data, efficacy is not assured. It will also be demonstrated that even within the same malignancy, what holds true in the metastatic setting does not necessarily apply to the adjuvant or neoadjuvant setting. This review will assess the current evidence for the use of targeted therapies utilizing these biomarkers in the context of gastric and gastroesophageal (GE) junction cancers.