Related Experiment Video
Updated: May 6, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Platelet-derived growth factor receptor alpha (PDGFRα) targeting and relevant biomarkers in ovarian carcinoma
Koji Matsuo1, Masato Nishimura2, Kakajan Komurov3
1Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Objective:
Platelet-derived growth factor receptor alpha (PDGFRα) is believed to be associated with cell survival. We examined (i) whether PDGFRα blockade enhances the antitumor activity of taxanes in ovarian carcinoma and (ii) potential biomarkers of response to anti-PDGFRα therapy.
Methods:
PDGFRα expression in 176 ovarian carcinomas was evaluated with tissue microarray and correlated to survival outcome. Human-specific monoclonal antibody to PDGFRα (IMC-3G3) was used for in vitro and in vivo experiments with or without docetaxel. Gene microarrays and reverse-phase protein arrays with pathway analyses were performed to identify potential predictive biomarkers.
Results:
When compared to low or no PDGFRα expression, increased PDGFRα expression was associated with significantly poorer overall survival of patients with ovarian cancer (P=0.014). Although treatment with IMC-3G3 alone did not affect cell viability or increase apoptosis, concurrent use of IMC-3G3 with docetaxel significantly enhanced sensitization to docetaxel and apoptosis. In an orthotopic mouse model, IMC-3G3 monotherapy had no significant antitumor effects in SKOV3-ip1 (low PDGFRα expression), but showed significant antitumor effects in HeyA8-MDR (high PDGFRα expression). Concurrent use of IMC-3G3 with docetaxel, compared with use of docetaxel alone, significantly reduced tumor weight in all tested cell lines. In protein ontology, the EGFR and AKT pathways were downregulated by IMC-3G3 therapy. MAPK and CCNB1 were downregulated only in the HeyA8-MDR model.
Conclusion:
These data identify IMC-3G3 as an attractive therapeutic strategy and identify potential predictive markers for further development.
Insights
Blocking platelet-derived growth factor receptor alpha (PDGFRα) with IMC-3G3 enhances taxane antitumor activity in ovarian cancer. High PDGFRα expression predicts poorer survival, and IMC-3G3 shows potential as a therapeutic strategy.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Platelet-derived growth factor receptor alpha (PDGFRα) is implicated in cell survival.
- The role of PDGFRα in ovarian carcinoma progression and its therapeutic potential remains under investigation.
Purpose of the Study:
- To evaluate if PDGFRα blockade enhances taxane efficacy in ovarian cancer.
- To identify biomarkers predictive of response to anti-PDGFRα therapy.
Main Methods:
- PDGFRα expression was assessed in 176 ovarian carcinomas using tissue microarrays.
- In vitro and in vivo studies utilized a human-specific anti-PDGFRα antibody (IMC-3G3) with or without docetaxel.
- Gene and protein expression analyses were performed to identify predictive biomarkers.
Main Results:
- Increased PDGFRα expression correlated with significantly poorer overall survival in ovarian cancer patients.
- Combined IMC-3G3 and docetaxel treatment enhanced docetaxel sensitization and apoptosis compared to IMC-3G3 alone.
- IMC-3G3 monotherapy demonstrated antitumor effects in high PDGFRα-expressing models, while combination therapy reduced tumor weight across tested cell lines.
- EGFR, AKT, MAPK, and CCNB1 pathways were modulated by IMC-3G3 therapy.
Conclusions:
- IMC-3G3 represents a promising therapeutic strategy for ovarian cancer.
- Potential predictive markers for anti-PDGFRα therapy were identified, warranting further investigation.
More Related Videos
10:35An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
14:25Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
Published on: May 20, 2014
