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Open AccessArticle

Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures

1
OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine Carl Gustav Carus Technische Universität Dresden, 01307 Dresden, Germany
2
Institute of Radiooncology—OncoRay, Helmholtz-Zentrum Dresden—Rossendorf, 01328 Dresden, Germany
3
Institute of Radiation Physics, Helmholtz-Zentrum Dresden—Rossendorf, 01328 Dresden, Germany
4
Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands
5
German Cancer Consortium, Partner Site Dresden: German Cancer Research Center, 69120 Heidelberg, Germany
6
Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(11), 3216; https://doi.org/10.3390/cancers12113216
Received: 10 October 2020 / Revised: 23 October 2020 / Accepted: 29 October 2020 / Published: 31 October 2020
(This article belongs to the Special Issue Recent Advances in Pancreatic Ductal Adenocarcinoma)
Due to higher precision and consequent sparing of normal tissue, pancreatic cancer patients might profit from proton beam radiotherapy, a treatment modality increasingly used. Since molecular data upon proton irradiation in comparison to standard photon radiotherapy are limited in pancreatic cancer, the aims of our study were to unravel differences in the effectiveness of photon versus proton irradiation and to exploit radiation type-specific molecular changes for radiosensitizing 3D PDAC cell cultures. Although protons showed a slightly higher effectiveness and a stronger induction of molecular alterations than photons, our results revealed a radiation-type independent sensitization of molecular-targeted agents selected according to the discovered molecular, radiation-induced alterations.
Pancreatic ductal adenocarcinoma (PDAC) is a highly therapy-resistant tumor entity of unmet needs. Over the last decades, radiotherapy has been considered as an additional treatment modality to surgery and chemotherapy. Owing to radiosensitive abdominal organs, high-precision proton beam radiotherapy has been regarded as superior to photon radiotherapy. To further elucidate the potential of combination therapies, we employed a more physiological 3D, matrix-based cell culture model to assess tumoroid formation capacity after photon and proton irradiation. Additionally, we investigated proton- and photon-irradiation-induced phosphoproteomic changes for identifying clinically exploitable targets. Here, we show that proton irradiation elicits a higher efficacy to reduce 3D PDAC tumoroid formation and a greater extent of phosphoproteome alterations compared with photon irradiation. The targeting of proteins identified in the phosphoproteome that were uniquely altered by protons or photons failed to cause radiation-type-specific radiosensitization. Targeting DNA repair proteins associated with non-homologous endjoining, however, revealed a strong radiosensitizing potential independent of the radiation type. In conclusion, our findings suggest proton irradiation to be potentially more effective in PDAC than photons without additional efficacy when combined with DNA repair inhibitors. View Full-Text
Keywords: PDAC; radiotherapy; photon irradiation; proton beam irradiation; 3D cell culture; molecular targeting; DNA repair; NHEJ PDAC; radiotherapy; photon irradiation; proton beam irradiation; 3D cell culture; molecular targeting; DNA repair; NHEJ
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MDPI and ACS Style

Görte, J.; Beyreuther, E.; Danen, E.H.J.; Cordes, N. Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures. Cancers 2020, 12, 3216.

AMA Style

Görte J, Beyreuther E, Danen EHJ, Cordes N. Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures. Cancers. 2020; 12(11):3216.

Chicago/Turabian Style

Görte, Josephine; Beyreuther, Elke; Danen, Erik H.J.; Cordes, Nils. 2020. "Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures" Cancers 12, no. 11: 3216.

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