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Borst GR, Kumareswaran R, Yücel H, et al. Neoadjuvant olaparib targets hypoxia to improve radioresponse in a homologous recombination-proficient breast cancer model. Oncotarget. 2017;8(50):87638-87646doi: 10.18632/oncotarget.20936.
Borst, G. R., Kumareswaran, R., Yücel, H., Telli, S., Do, T., McKee, T., Zafarana, G., Jonkers, J., Verheij, M., O'Connor, M. J., Rottenberg, S., & Bristow, R. G. (2017). Neoadjuvant olaparib targets hypoxia to improve radioresponse in a homologous recombination-proficient breast cancer model. Oncotarget, 8(50), 87638-87646. https://doi.org/10.18632/oncotarget.20936
Borst, Gerben R, et al. "Neoadjuvant olaparib targets hypoxia to improve radioresponse in a homologous recombination-proficient breast cancer model." Oncotarget vol. 8,50 (2017): 87638-87646. doi: https://doi.org/10.18632/oncotarget.20936
Borst GR, Kumareswaran R, Yücel H, Telli S, Do T, McKee T, Zafarana G, Jonkers J, Verheij M, O'Connor MJ, Rottenberg S, Bristow RG. Neoadjuvant olaparib targets hypoxia to improve radioresponse in a homologous recombination-proficient breast cancer model. Oncotarget. 2017 Sep 15;8(50):87638-87646. doi: 10.18632/oncotarget.20936. eCollection 2017 Oct 20. PMID: 29152107; PMCID: PMC5675659.
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Oncotarget. 2017 Sep 15;8(50):87638-87646. doi: 10.18632/oncotarget.20936. eCollection 2017 Oct 20.

Neoadjuvant olaparib targets hypoxia to improve radioresponse in a homologous recombination-proficient breast cancer model.

Oncotarget

Gerben R Borst, Ramya Kumareswaran, Hatice Yücel, Seyda Telli, Trevor Do, Trevor McKee, Gaetano Zafarana, Jos Jonkers, Marcel Verheij, Mark J O'Connor, Sven Rottenberg, Robert G Bristow

Affiliations

  1. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
  2. Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Canada.
  3. Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiation Oncology, Amsterdam, The Netherlands.
  4. Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Molecular Biology, Amsterdam, The Netherlands.
  5. Oncology, Innovative Medicines and Early Development, AstraZeneca, Cambridge, United Kingdom.
  6. Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

PMID: 29152107 PMCID: PMC5675659 DOI: 10.18632/oncotarget.20936

Abstract

Clinical trials are studying the benefits of combining the PARP-1 inhibitor olaparib with chemotherapy and radiotherapy treatment in a variety of cancer increasing the therapeutic ratio for olaparib may come from its ability to modify the tumour microenvironment by targeting homologous recombination-deficient, hypoxic tumour clonogens, and/or increasing tumour-associated vasodilation to improve oxygenation. Herein, we investigated the effect of prolonged neoadjuvant exposure to olaparib on the tumor microenvironment using a genetically-engineered mouse p53-/- syngeneic breast cancer model, which is proficient in homology-directed DNA repair. We observed increased

Keywords: hypoxia; neoadjuvant treatment; olaparib; radiotherapy; targeted therapy

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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