Emerging biological drugs for the treatment of gastroesophageal adenocarcinoma

INTRODUCTION: Gastric cancer (GC) and gastroesophageal junction cancer (GOJC) patients have a poor prognosis with a 5-year relative survival rate of 6% in the metastatic setting. Despite the well-characterized molecular features, patients have been historically considered for treatment with universal and undistinguishing chemotherapies and targeted agents, except for the HER2-positive population and some immunological approaches. AREAS COVERED: In this review, we discuss the intrinsic characteristics of GC/GOJC from an epidemiological, molecular, and clinical perspective with an exhaustive evaluation of the reported and ongoing phase II/III clinical trials with targeted therapies. EXPERT OPINION: The absence of robust biomarkers, the difficulties in measuring it due to the well-recognized molecular heterogeneity, and in part nonoptimistic clinical trial designs have been a major cause of frequent failure. Current efforts should focus on proper recognition of the distinctive molecular and clinical features of each GC/GOJC patient. Sequencing both tumor tissue DNA and ctDNA could identify targetable alterations, including rare alterations, thus allowing GC/GOJC patients for a precision medicine benefit.