Dual targeting of IGF-1R and ErbB3 as a potential therapeutic regimen for ovarian cancer
| Autor: | Sergio Iadevaia, Michael D. Curley, Birgit Schoeberl, Adam Camblin, Gege Tan, Alexey Lugovskoy, Chrystal U. Louis, Mari Mino-Kenudson, Vasileios Askoxylakis, Troy Bloom, Victoria Rimkunas, Isabel Yannatos, Daryl C. Drummond |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cell signaling
Paclitaxel Receptor ErbB-3 Cell Survival medicine.medical_treatment lcsh:Medicine Antineoplastic Agents Antibodies Monoclonal Humanized Article Receptor tyrosine kinase Polyethylene Glycols Receptor IGF Type 1 Mice Growth factor receptor Ovarian cancer Cell Line Tumor medicine Animals Humans ERBB3 Epidermal growth factor receptor lcsh:Science Cell Proliferation Ovarian Neoplasms Chemotherapy Multidisciplinary biology business.industry lcsh:R Cancer Drug Synergism medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Cancer therapeutic resistance Doxorubicin Drug Resistance Neoplasm biology.protein Cancer research lcsh:Q Female Cisplatin business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Therapeutically targeting receptor tyrosine kinases has proven to be paramount to overcoming chemotherapy resistance in several cancer indications, improving patient outcomes. Insulin-Like Growth Factor Receptor 1 (IGF-1R) and Epidermal Growth Factor Receptor 3 (ErbB3) have been implicated as two such drivers of resistance, however their simultaneous role in ovarian cancer chemotherapy resistance remains poorly elucidated. The aim of this work is to determine the effects of dual IGF-1R/ErbB3 inhibition on ovarian cancer cell signaling, growth, and in vivo efficacy. Assessment of in vitro chemotherapy response across a panel of ovarian cancer cell lines revealed that increased IGF-1R cell surface expression correlates with decreased sensitivity to chemotherapy, and that growth induced by IGF-1R and ErbB3 ligands is blocked by the tetravalent bispecific antibody targeting IGF-1R and ErbB3, istiratumab. In vitro chemotherapy treatment increased ovarian cancer cell line capacity to activate prosurvival PI3K signaling in response to ligand, which could be prevented with istiratumab treatment. Furthermore, in vivo efficacy of standard of care chemotherapies using a xenograft model of ovarian cancer was potentiated with istiratumab. Our results suggest a role for IGF-1R and ErbB3 in driving chemotherapy resistance of ovarian cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|