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Updated: Jun 30, 2026
Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology
Published on: March 24, 2015
Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy
Gary Guishan Xiao1, Bing-Sen Zhou, George Somlo
1Department of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CA 91010-3000, USA.
Background:
The expression and activity of ribonucleotide reductase (RR) has been associated with resistance to multiple drugs in human cancer. The use of antisense oligonucleotide drug, GTI-2040, a 20-mer phosphorothioate oligonucleotide complemented to the human RR M2 subunit mRNA, represents an effective strategy for inhibiting RR. The increased specificity due to the anti-resistance effect of GTI-2040 may also lead to a more favorable therapeutic outcome.
Materials And Methods:
To understand the molecular mechanism underlying RR inhibition, patients' blood samples were analyzed using multiple dimensional proteomics technology via matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry.
Results:
A major difference occurred at 5k m/z in the MALDI profile, which appeared only in the non-responsive group and diminished after GTI-2040 treatment. This specific peptide peak remained at the basal level in responsive patients. The peak was identified to represent the F-box/LLR-repeat protein 17 (FBXL17) through nanoelectrospray ionization liquid chromatography-tandem mass spectrometry (nanoESI LC-MS/MS). Further characterization revealed that FBXL17 [corrected] directly interacts with the human RR M2 (RRM2) subunit to promote hRRM2 overexpression in the breast cancer cell line MCF-7.
Conclusion:
Validation of this protein using real-time RT-PCR indicates the F-box protein 17 (FBXL17) can serve as a therapeutic target and surrogate marker for breast cancer therapy.
Insights
The F-box protein 17 (FBXL17) is identified as a key factor in drug resistance in breast cancer. Targeting FBXL17 may improve therapeutic outcomes for patients resistant to standard treatments.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Ribonucleotide reductase (RR) expression and activity are linked to multidrug resistance in human cancers.
- GTI-2040, an antisense oligonucleotide targeting RR M2 subunit mRNA, is an effective strategy for RR inhibition.
- This drug may offer improved therapeutic outcomes due to its anti-resistance effects.
Purpose of the Study:
- To elucidate the molecular mechanisms of RR inhibition by GTI-2040.
- To identify biomarkers associated with response to GTI-2040 treatment.
- To explore novel therapeutic targets for breast cancer.
Main Methods:
- Proteomic analysis of patient blood samples using MALDI-TOF mass spectrometry.
- Identification of differentially expressed peptides via nanoESI LC-MS/MS.
- Validation of protein expression using real-time RT-PCR.
Main Results:
- A specific peptide peak at 5k m/z, identified as F-box/LLR-repeat protein 17 (FBXL17), was present in non-responsive patients and diminished after GTI-2040 treatment.
- FBXL17 directly interacts with the human RR M2 (RRM2) subunit, promoting hRRM2 overexpression in MCF-7 breast cancer cells.
- FBXL17 levels correlated with drug response, remaining basal in responsive patients.
Conclusions:
- FBXL17 is a potential therapeutic target for breast cancer.
- FBXL17 can serve as a surrogate marker for predicting response to breast cancer therapy.
- Targeting FBXL17 may overcome drug resistance and improve treatment efficacy.
