A Fluorescent Probe Targeting EGFR for the Stratification of Prostate Cancer Cells

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Effective cancer patient stratification is crucial for evaluating therapeutic strategies but remains challenging.
• The epidermal growth factor receptor (EGFR) kinase is a key oncogenic target in various cancers.

Purpose of the Study:

• To design and validate a novel fluorescent probe for targeting and characterizing EGFR kinase activity.
• To utilize the probe for subtyping prostate cancer patient samples and identifying novel EGFR mutations.

Main Methods:

• Development of a competitive, modular fluorescent probe targeting EGFR kinase.
• Assessment of probe's ability to inhibit EGFR activity, label EGFR-overexpressing cells via flow cytometry, and bind to EGFR mutants.
• Application of probe-based cytometry to subtype urine samples from prostate cancer patients.

Main Results:

• The fluorescent probe demonstrated dose-dependent inhibition of EGFR kinase activity.
• The probe selectively labeled EGFR-overexpressing cells and sensitively bound to EGFR oncogenic mutants.
• Analysis of prostate cancer patient samples revealed distinct probe responses based on EGFR expression levels, leading to the identification of three novel EGFR mutations, including V745M, in a castration-resistant metastatic case.

Conclusions:

• The developed fluorescent probe is a valuable tool for EGFR-targeted cancer research and patient stratification.
• Probe-based cytometry can aid in identifying novel oncogenic mutations in challenging cancer cases, such as castration-resistant prostate cancer.