In Silico Screening and Validation of PDGFRA Inhibitors Enhancing Radioiodine Sensitivity in Thyroid Cancer

Aberrant activation of platelet-derived growth factor receptor alpha (PDGFRA) has been implicated in tumorigenesis and radioiodine resistance of thyroid cancer, indicating its therapeutic potential. In the present study, we confirmed the association between PDGFRA and radioiodine resistance in thyroid cancer using bioinformatics analysis and constructed a prediction model of PDGFRA inhibitors using machine learning and molecular docking approaches. We then performed a virtual screening of a traditional Chinese medicine (TCM) derived compound library and successfully identified 4',5,7-trimethoxyflavone as a potential PDGFRA inhibitor. Further characterization revealed a significant inhibitory effect of 4',5,7-trimethoxyflavone on PDGFRA-MAPK pathway activation, and that it could upregulate expression of sodium iodide symporter (NIS) as well as improve radioiodine uptake capacity of radioiodine-refractory thyroid cancer (RAIR-TC), suggesting it a potential drug lead for the development of new RAIR-TC therapy.

Automated summary

This study confirmed the association between PDGFRA and radioiodine resistance in thyroid cancer and developed a prediction model of PDGFRA inhibitors using bioinformatics analysis, machine learning, and molecular docking. A potential PDGFRA inhibitor was identified from a traditional Chinese medicine compound library, which showed significant inhibitory effects on PDGFRA-MAPK pathway activation and improved radioiodine uptake capacity in radioiodine-refractory thyroid cancer.