Cancer cells can change their identity to survive harsh conditions, a phenomenon known as cell plasticity. This ability allows cancer cells to adapt, resist treatment, and spread to other body parts. In gastric cancer (GC), one of the deadliest cancers worldwide, this plasticity plays a significant role in why treatments often fail. However, scientists still do not fully understand how cancer cells switch between different cell states and what drives these changes. To address this, we use patient-derived organoids (PDOs) — tiny 3D models grown from actual human tumors — to study how cancer cells respond to different treatments. By applying a cutting-edge gene-editing technology called CRISPR interference (CRISPRi), we can selectively turn off specific genes that regulate cell identity and observe how cancer cells change over time. We will also use single-cell sequencing to analyze thousands of individual cancer cells and map their responses to different gene changes. Our goal is to uncover which genes drive cancer cells to become drug-resistant and how they evolve to escape treatment. This research could lead to new strategies to prevent drug resistance, helping doctors develop better treatments that stop cancer from adapting and make therapies more effective.