A Fluorescent Probe Targeting EGFR for the Stratification of Prostate Cancer Cells
Xingxing Wang1, Peng Liu1, Linli Li1
1School of Life Sciences, Faculty of Medicine, Tianjin University, Tianjin 300072, PR China.
Abstract:
Effective stratification of cancer patients is critical yet challenging for evaluating therapeutic strategies. In this study, we designed a competitive, modular fluorescent probe targeting the oncogenic epidermal growth factor receptor (EGFR) kinase. This probe specifically inhibits EGFR kinase activity in a dose-dependent manner, selectively labels EGFR-overexpressing cells in flow cytometry, and sensitively binds to EGFR oncogenic mutants. Utilizing probe-based cytometry to subtype urine samples from prostate cancer patients, we discovered that samples with overexpressed wild-type EGFR did not respond sensitively to the probe, aligning with findings from an early multi-center clinical study. Notably, one sample with low EGFR expression exhibited the highest sensitivity to the probe, leading to the identification of three non-characterized mutations, including the activating mutation V745M, on the EGFR kinase. This case involved a tumor that had progressed to the castration-resistant metastatic stage.
Insights
A novel fluorescent probe precisely targets epidermal growth factor receptor (EGFR) kinase, aiding in cancer patient stratification. This probe identified new EGFR mutations in a castration-resistant prostate cancer case.
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.
