Brave new world—new and emerging treatments for gastric cancer

Abstract: Despite considerable international heterogeneity in the incidence and histological subtypes of gastric cancer (GC), in addition to more recent epidemiological trends, chemotherapy has long represented the main systemic therapeutic option in its treatment. For the roughly 20% of GC with human epidermal growth factor receptor 2 (HER2) overexpression, there is a more recently established role for the addition of HER2+ based therapy in the form of trastuzumab. However, while immune checkpoint inhibitors (ICIs) have revolutionised the treatment of other malignancies including melanoma and renal cell carcinoma over the past decade, they have only gained a foothold in GC in more recent years. This article reviews the existing evidence for ICIs in GC as a novel therapeutic option. It also looks to ongoing trials of immune checkpoint inhibition both in the perioperative and advanced setting, and in combination with other therapeutic targets including HER2+. Other investigational immune based therapies including chimeric antigen receptor T-cell (CAR-T) therapy and anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (anti-TIGIT) therapy are considered, in addition to reviewing the building evidence for alternative therapeutic targets currently under investigation in GC, including fibroblast growth factor receptor 2b (FGFR2b) and claudin 18.2 amongst others. These novel and evolving targets represent a brave new world in therapeutic intervention in GC, with the potential to transform outcomes for patients internationally.