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Updated: Apr 30, 2026
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Evaluation of Tissue from Patients with Prostate Cancer Identifies B7-H3 as an Androgen-Regulated, Broadly Expressed,
Shivang Sharma1, Nikita Mundhara1, Emirhan Tekoglu2,3
1Department of Oncology, Johns Hopkins School of Medicine; Baltimore, Maryland.
Purpose:
Advanced prostate cancer management suffers from therapeutic resistance due to naturally transient or androgen receptor (AR)-dependent expression of clinically actionable surface targets. We aimed to identify the most promising clinically relevant prostate cancer targets using RNA and protein expression levels across the prostate cancer continuum-hormone-sensitive, castration-resistant, neuroendocrine, and "double-negative" prostate cancer.
Experimental Design:
We performed integration of a large single-cell transcriptomics atlas (JHU-PANORAMA, ∼1 million cells and 213 patients) and patient-derived xenograft models for the systematic investigation of the clinically relevant surfaceome, followed by proteomic validation on patient samples and mechanistic investigations on prostate cancer cell lines and patient samples.
Results:
B7 homolog 3 (B7-H3) was found to be the most uniformly expressed across the entire prostate cancer continuum. JHU-PANORAMA is made available for interactive visualization as an R Shiny web app. Further mitigation of therapeutic resistance is proposed through a systematic framework for bispecific antibody design, in which B7-H3 demonstrates high combinatorial scores with TROP-2, NECTIN1, KLK2, and NECTIN4. B7-H3 was also shown to be negatively regulated by AR and synergistically inhibit tumor growth when combined with androgen inhibition.
Conclusions:
B7-H3 demonstrates low interpatient and intratumoral heterogeneity, with significant synergistic effects in combination with AR inhibition. These properties could uniquely position B7-H3 as a broad-spectrum therapeutic target, with the potential to combine B7-H3 based therapeutics with standard androgen deprivation therapy for synergistic effects to overcome therapeutic resistance across the prostate cancer disease continuum. See related article by Makovec et al., p. 3381.
Insights
B7-H3 is a promising target for advanced prostate cancer (PCa) management, showing uniform expression across all disease stages. Combining B7-H3 therapies with androgen deprivation therapy (ADT) may overcome treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Advanced prostate cancer (PCa) presents therapeutic resistance due to variable expression of surface targets.
- Identifying reliable targets across the PCa continuum is crucial for effective management.
Purpose of the Study:
- To identify the most promising, clinically relevant surface targets for advanced prostate cancer (PCa).
- To evaluate targets across hormone-sensitive, castration-resistant, neuroendocrine, and double-negative PCa (DNPC) subtypes.
Main Methods:
- Integrated single-cell transcriptomics (JHU-PANORAMA, ~1 million cells, 213 patients) and patient-derived xenograft (PDX) models.
- Proteomic validation on patient samples and mechanistic studies on PCa cell lines.
Main Results:
- B7-H3 exhibited the most uniform expression across the entire PCa continuum.
- B7-H3 showed high potential for bispecific antibody design, particularly with TROP-2, NECTIN1, KLK2, and NECTIN4.
- B7-H3 expression is negatively regulated by androgen receptor (AR), and its combination with AR inhibition synergistically reduced tumor growth.
Conclusions:
- B7-H3 demonstrates low heterogeneity, making it a robust therapeutic target.
- B7-H3-based therapies combined with androgen deprivation therapy (ADT) offer a synergistic approach to overcome resistance in advanced PCa.
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