Image-Based Phenotypic Profiling Enables Rapid and Accurate Assessment of EGFR-Activating Mutations in Tissues from Lung Cancer Patients.

Summary

A covalent, quenched TKI-derived probe enables no-wash, real-time imaging of mutant EGFR, distinguishing mutant from wild-type tumors in vivo and predicting EGFR mutations in patient tissues with 94% accuracy (98% with IHC). This phenotypic imaging approach complements or accelerates DNA-based testing and may streamline EGFR-TKI decision-making.

Key Findings

• Designed a covalent, quenched EGFR-TKI probe enabling no-wash real-time imaging of EGFR in living cells.
• Distinguished EGFR-mutant from wild-type tumors in mice via fluorescence intensity with high contrast.
• Predicted EGFR mutations in patient tumor tissues with 94% accuracy; 98% when integrated with IHC.

Clinical Implications

If validated prospectively, this probe could complement or, in some settings, precede sequencing to rapidly stratify patients for EGFR-TKI therapy from biopsy material, especially when tissue is limited or turnaround time is critical.

Limitations

• Clinical validation sample size not specified and likely limited; prospective, multicenter studies are needed.
• May not capture rare/complex EGFR alterations or co-mutations; requires viable tissue and imaging infrastructure.

Future Directions

Prospective head-to-head comparisons with NGS in diverse cohorts; expansion to resistance mutations and other oncogenic kinases; workflow integration for real-world turnaround and cost-effectiveness.