A novel strategy for PDGFRβ detection and TKI therapy monitoring

Research Background

Targeted therapy represented by EGFR is a crucial approach for solid tumors such as glioma, but acquired drug resistance frequently occurs after treatment. Drug resistance is the primary factor limiting the efficacy of clinical targeted therapy for tumors. The development of detection technologies capable of dynamically monitoring tumor drug resistance can timely guide the adjustment of therapeutic strategies and improve patient prognosis, representing a key breakthrough in overcoming clinical therapeutic bottlenecks.

Research Progress 

Traditional detection methods (Western blot, ELISA, IHC) are cumbersome, time-consuming, and end-point assays, which make it difficult to achieve real-time dynamic monitoring and fail to meet the clinical demands for rapid efficacy evaluation and early drug resistance warning.  Recent studies have confirmed that abnormal upregulation of PDGFRβ serves as a key bypass pathway mediating tumor resistance to EGFR-TKIs, and its dynamic expression changes can directly reflect the process of tumor adaptive drug resistance.

The team verified that TKIs such as erlotinib and gefitinib can significantly induce PDGFRβ upregulation, and its dynamic expression changes directly reflect the progression of tumor adaptive drug resistance in glioma cell models. The team constructed a Cy3 fluorescently labeled PDGFRβ aptamer-functionalized black phosphorus nanoprobe, which realizes specific recognition and quantitative detection of PDGFRβ relying on the "fluorescence quenching-recovery" switching mechanism, establishing a novel method for dynamic monitoring of PDGFRβ during TKI treatment.

Experiments confirmed that knockdown of PDGFRβ can effectively reverse TKI resistance and significantly enhance the apoptosis-inducing effect of erlotinib on drug-resistant glioma cells, providing experimental support for the synergistic therapeutic strategy of "EGFR-TKI combined with PDGFRβ inhibition".

Future Prospects

This nano-fluorescence switching strategy provides a universal technical paradigm for dynamic monitoring of tumor targets, which can be extended to the detection of more drug resistance-related receptors in the future. The team will further optimize the targeting and circulation stability of the probe, promote its development as a novel precise diagnostic tool for intraoperative navigation, efficacy evaluation, and drug resistance warning, and provide key technical support for individualized tumor therapy.

Sources: https://spj.science.org/doi/10.34133/research.1218