Utilizing gastric cancer organoids to assess tumor biology and personalize medicine

Abstract

While the incidence and mortality of gastric cancer (GC) have declined due to public health programs, it remains the third deadliest cancer worldwide. For patients with early disease, innovative endoscopic and complex surgical techniques have improved survival. However, for patients with advanced disease, there are limited treatment options and survival remains poor. Therefore, there is an urgent need for more effective therapies. Since novel therapies require extensive preclinical testing prior to human trials, it is important to identify methods to expedite this process. Traditional cancer models are restricted by the inability to accurately recapitulate the primary human tumor, exorbitant costs, and the requirement for extended periods of development time. An emerging in vitro model to study human disease is the patient-derived organoid, which is a three-dimensional system created from fresh surgical or biopsy tissues of a patient’s gastric tumor. Organoids are cultured in plastic wells and suspended in a gelatinous matrix, providing a substrate for extension and growth in all dimensions. They are rapid-growing and highly representative of the molecular landscape, histology, and morphology of the various subtypes of GC. Organoids uniquely model tumor initiation and growth, including steps taken by normal stomach cells to transform into invasive, intestinal-type tumor cells. Additionally, they provide ample material for biobanking and screening novel therapies. Lastly, organoids are a promising model for personalized therapy and warrant further investigation in drug sensitivity studies for GC patients.

Keywords: Organoids, Gastric cancer, Cancer models, Drug sensitivity, Drug screening, Personalized medicine

Core tip: Patient-derived organoids are three-dimensional models of human cancer useful for investigating tumor biology and drug discovery. There are now many reports on the utility of organoids in cancer research and personalized therapy. However, none focus on the use of organoid technology in improving outcomes for patients with gastric cancer (GC), which is one of the deadliest cancers worldwide. Our objective is to report the current progress in GC organoid technology in comparison to traditional cancer models and evaluate their potential role in informing personalized clinical decision making for patients with GC.