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Updated: Jan 5, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer
Vikram B Wali1, Gauri A Patwardhan2, Vasiliki Pelekanou3
1Department of Internal Medicine, Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA. walivik@gmail.com.
Abstract:
The goal of this study was to identify a novel target for antibody-drug conjugate (ADC) development in triple negative breast cancer (TNBC), which has limited treatment options, using gene expression datasets and in vitro siRNA/CRISPR and in vivo functional assays. We analyzed 4467 breast cancers and identified GABRP as top expressed gene in TNBC with low expression in most normal tissues. GABRP protein was localized to cell membrane with broad range of receptors/cell (815-53,714) and expressed by nearly half of breast cancers tissues. GABRP gene knockdown inhibited TNBC cell growth and colony formation in vitro and growth of MDA-MB-468 xenografts in nude mice. Commercially available anti-GABRP antibody (5-100 μg/ml) or de novo generated Fabs (20 μg/ml) inhibited TNBC cell growth in vitro. The same antibody conjugated to mertansine (DM1) also showed significant anticancer activity at nanomolar concentrations. Our results indicate that GABRP is a potential novel therapeutic target for ADC development.
Insights
Researchers identified GABRP as a promising target for antibody-drug conjugate (ADC) therapy in triple-negative breast cancer (TNBC). GABRP targeting inhibited tumor growth, suggesting its potential for new cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Triple-negative breast cancer (TNBC) presents limited therapeutic options.
- Novel therapeutic targets are crucial for improving TNBC treatment outcomes.
Purpose of the Study:
- To identify a novel target for antibody-drug conjugate (ADC) development in TNBC.
- To evaluate the therapeutic potential of targeting GABRP in TNBC.
Main Methods:
- Analysis of gene expression datasets from 4467 breast cancers.
- In vitro siRNA/CRISPR gene knockdown and functional assays.
- In vivo xenograft studies and antibody-based inhibition assays.
Main Results:
- GABRP was identified as the top expressed gene in TNBC with low expression in normal tissues.
- GABRP protein is cell membrane-localized and broadly expressed in breast cancers.
- GABRP knockdown and anti-GABRP antibodies inhibited TNBC cell growth and xenograft tumor growth.
- GABRP-DM1 ADC demonstrated significant anticancer activity at nanomolar concentrations.
Conclusions:
- GABRP is a potential novel therapeutic target for ADC development in TNBC.
- Targeting GABRP shows promise for effective treatment strategies against TNBC.
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