Overcoming tumor resistance in gastric cancer may require a multifaceted approach. Combination therapies involving CAR T cells and other immunomodulatory agents, such as immune checkpoint inhibitors or cytokine therapies, can synergistically enhance anti-tumor responses. Careful consideration of the temporal sequence and dosing regimens is crucial to maximize therapeutic efficacy while minimizing potential toxicities. Precision medicine aims to tailor treatment strategies based on the unique genetic and molecular characteristics of individual tumors. Genetic profiling of gastric cancer patients can identify specific alterations contributing to resistance, allowing for the development of personalized CAR T cell therapies. Strategies such as CRISPR-based genome editing may be employed to address genetic alterations contributing to EpCAM downregulation or antigenic heterogeneity [4].
Several clinical trials are underway to evaluate the safety and efficacy of EpCAM-targeted CAR T cell therapies in gastric cancer. These trials are designed to assess the impact of various modifications, including the use of third-generation CAR constructs, co-stimulatory molecules, and alternative antigen targeting strategies. The results of these trials will provide crucial insights into the clinical feasibility and potential of CAR T cell therapy for gastric cancer. The dynamic landscape of cancer research underscores the importance of continuous innovation. Future directions in CAR T cell therapy for gastric cancer may involve the development of next-generation CAR constructs with improved functionality and resistance to tumor evasion mechanisms. Integration of synthetic biology approaches, such as logic-gated CAR T cells, may enable enhanced precision and control over therapeutic responses. Additionally, advancements in gene-editing technologies and synthetic biology hold the potential to address genetic alterations contributing to tumor resistance [5].
Ethical considerations in the development and application of EpCAMtargeted CAR T cell therapy in gastric cancer are paramount. Patient selection should be guided by rigorous criteria, considering factors such as tumor characteristics, prior treatments, and potential risks associated with the therapy. Informed consent processes should be comprehensive, ensuring that patients and their families have a clear understanding of the experimental nature of the treatment, potential benefits, and associated risks. As with any advanced therapeutic intervention, the monitoring and management of adverse events are critical. Cytokine release syndrome (CRS), neurotoxicity, and off-target effects are potential complications associated with CAR T cell therapy. Close monitoring of patients during and after treatment, coupled with proactive management strategies, is essential for ensuring patient safety. Ongoing research focused on mitigating adverse events and improving the safety profile of CAR T cell therapies contributes to the ethical application of these innovative treatments [6].