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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4162 - ODM-207 - a novel BET bromodomain inhibitor with antitumor activity in nonclinical models of ER+ breast cancer

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Anu Moilanen

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

A. Moilanen1, J. Lindqvist2, M. Björkman1, R. Riikonen1, D. Nicorici1, E. Mattila1, C. Abbineni3, M. Jaleel3, J. Eriksson4, P. Kallio2

Author affiliations

  • 1 Orion Corporation, Orion Pharma, 02100 - Espoo/FI
  • 2 Orion Corporation, Orion Pharma, Espoo/FI
  • 3 Aurigene Discovery Technologies Limited, Aurigene Discovery, Bangalore/IN
  • 4 Åbo Akademi University, University of Turku, Turku/FI
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Resources

Abstract 4162

Background

The bromodomain and extraterminal (BET) family of proteins are chromatin readers that promote the transcription of several important cell identity genes. BET inhibitors have shown promising antitumor activity in a variety of pre-clinical cancer models, as BET inhibition abrogates the transcription of several key oncogenes in a cell type-specific manner. Hence, the purpose of this study was to determine the anticancer activity of the novel BET inhibitor ODM-207 in ER+ breast cancer models and to look for cancer-associated signaling pathways suppressed by BET inhibitors.

Methods

ER+ breast cancer cell lines were studied for sensitivity to ODM-207 and the in vivo efficacy was assessed using the ER+ Ma3366 patient-derived xenograft model. For gene expression analyses, breast cancer cells were treated with ODM-207 or reference BET inhibitor JQ1 and differentially expressed genes were analysed by RNA-sequencing. The ability of ODM-207 to regulate anticancer signaling pathways was validated by western blotting. Synergistic drug interactions were profiled using five-concentration dose response matrices.

Results

ODM-207 is a novel BET inhibitor structurally distinct from JQ1 and its benzodiazepine-related derivatives. In this study, we show that ODM-207 effectively inhibits the proliferation of ER+ breast cancer cell lines as well as suppresses the growth of patient-derived xenograft tumors. Furthermore, ODM-207 and the JQ1 targeted several pathways important for cancer progression such as the DNA damage and repair pathways.

Conclusions

Our results indicate that ODM-207, which is currently in Phase I clinical trials for treating solid tumors, causes significant growth inhibition in pre-clinical models of ER+ breast cancer, and regulates signaling pathways involved in breast cancer cell survival.

Clinical trial identification

Legal entity responsible for the study

Orion Corporation, Orion Pharma.

Funding

Orion Corporation, Orion Pharma.

Disclosure

A. Moilanen, M. Björkman, R. Riikonen, D. Nicorici, E. Mattila, P. Kallio: Employee: Orion Corporation, Orion Pharma. J. Lindqvist: Employee: Orion Corporation, Orion Pharma, Åbo Akademi University. C. Abbineni, M. Jaleel: Employee: Aurigene Discovery Technologies Limited. J. Eriksson: Employee: Åbo Akademi.

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