Feasibility of Endoscopic Gastric Cancer Organoids to Optimize Neoadjuvant Chemotherapy

Patients with locally advanced gastric cancer are candidates to receive neo-adjuvant chemotherapy prior to surgical resection of their disease. The rationale for this treatment approach was established from a phase III randomized controlled trial demonstrating an overall survival benefit with neoadjuvant chemotherapy. However, the majority of patients (approximately 60%) do not benefit from neoadjuvant chemotherapy and are unnecessarily exposed to adverse events from cytotoxic chemotherapies. The objective of our project is to determine whether a newly developed patient derived cancer model (i.e., organoids) can be used to select the drug that is most likely to work for neoadjuvant therapy. Organoids are 3-D cancer models (i.e., miniature organs) grown in culture that accurately recapitulate human disease and have tremendous potential to provide accurate drug sensitivity testing. Our laboratory has successfully developed organoids from endoscopic biopsies of gastric cancer and we have demonstrated drug sensitivity testing with these models (manuscript submitted for publication). Our goal within the next 1-2 years is to organize a multicenter trial using organoids to select optimal chemotherapy for neoadjuvant chemotherapy for patients with locally advanced gastric cancer.