Fibroblast Activation Protein Inhibitor-Based Radionuclide Therapies: Current Status and Future Directions

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor-based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor-based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.

Automated summary

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer-associated fibroblasts play a crucial role in tumor growth, invasion, metastasis, and treatment resistance. Fibroblast activation protein (FAP) inhibitor-based radionuclide therapies show promise in cancer diagnosis and treatment, but their success has been suboptimal in clinical trials. This review summarizes preclinical and clinical FAP-based radionuclide therapies and discusses their potential for future research and clinical decision-making.