Abstract | OBJECTIVE: 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.
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Authors | Koji Matsuo, Masato Nishimura, Kakajan Komurov, Mian M K Shahzad, Rouba Ali-Fehmi, Ju-Won Roh, Chunhua Lu, Dianna D Cody, Prahlad T Ram, Nick Loizos, Robert L Coleman, Anil K Sood |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 132
Issue 1
Pg. 166-75
(Jan 2014)
ISSN: 1095-6859 [Electronic] United States |
PMID | 24183729
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © 2013. |
Chemical References |
- Antibodies, Monoclonal
- Biomarkers
- Taxoids
- Docetaxel
- Receptor, Platelet-Derived Growth Factor alpha
- Proto-Oncogene Proteins c-akt
- olaratumab
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Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Apoptosis
(drug effects)
- Biomarkers
- Docetaxel
- Female
- Humans
- Mice
- Ovarian Neoplasms
(chemistry, drug therapy, mortality)
- Proto-Oncogene Proteins c-akt
(physiology)
- Receptor, Platelet-Derived Growth Factor alpha
(analysis, antagonists & inhibitors)
- Signal Transduction
- Taxoids
(therapeutic use)
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