Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Simple Summary Gastric and esophageal cancers often present at an advanced stage at diagnosis, which negatively impacts a patient's survival. While treatment options exist, at that point, they are palliative in nature and prioritize improving survival and quality of life. The treatment paradigm for the advanced disease have been consistently changing in the right direction, but several unmet needs still exist. In response, ongoing studies are revolutionizing the approach taken to treat these cancers by focusing on targeted therapies. Current and future research aim to exploit the mechanisms responsible for enhancing cancerous growth and metastasis in order to improve patient outcomes. Together, gastric cancer and esophageal cancer (EC) possess two of the highest incidence rates amongst all cancers. They exhibit poor prognoses in which the 5-year survival rate is dismal. In addition to cytotoxic chemotherapy, treatment efforts have been geared toward targeting human epidermal growth factor receptor 2 (HER-2), vascular endothelial growth factor (VEGF), and programmed death ligand-1 (PD-1). Although ample success has been recorded with these agents, gastric and esophageal cancer remain lethal, and further research into potential treatment alternatives is needed. In this article, we will review some of the targets at the forefront of investigation such as claudin, Dickkopf-related protein 1 (DKK-1), fibroblast growth factor receptor (FGFR), and matrix metalloproteinases (MMPs). These innovative target pathways are in the midst of clinical trials to be implemented in the treatment algorithm for this patient population. Ultimately, exploiting the oncogenic tendencies of these potential biomarkers creates an opportunity for precise treatment and improved prognosis for these cancers. Lastly, research aimed toward reversing PD-1 antibodies resistance by combining it with other novel agents or other treatment modalities is underway in order to expand existing treatment options for this patient population.

Automated summary

Gastric and esophageal cancers are often diagnosed at an advanced stage, leading to poor prognoses. Treatment options prioritize improving survival and quality of life, with ongoing research focusing on targeted therapies to exploit oncogenic tendencies and enhance patient outcomes. The development of new treatment alternatives and the investigation of potential biomarkers aim to address the unmet needs of these lethal cancers.