Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures.
Comparative Proton and Photon Irradiation Combined with Pharmacological Inhibitors in 3D Pancreatic Cancer Cultures.
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DOI：
10.3390/cancers12113216
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发表时间：
2020-10-31
期刊：
影响因子：
5.2
通讯作者：
Cordes N
中科院分区：
文献类型：
--
作者：
Görte J;Beyreuther E;Danen EHJ;Cordes N
由于更高的精度和随之而来的正常组织的保留，胰腺癌患者可能会受益于质子束放射治疗，治疗方式越来越多地使用。由于质子照射与标准光子放射治疗相比在胰腺癌中的分子数据有限，我们研究的目的是解开光子与质子照射的有效性差异，并利用放射增敏3D PDAC细胞培养物的辐射类型特异性分子变化。虽然质子表现出比光子稍高的有效性和更强的诱导分子改变，我们的研究结果显示，根据发现的分子，辐射诱导的改变选择的分子靶向剂的辐射类型独立敏化。胰腺导管腺癌（PDAC）是一种高度耐药的肿瘤实体，其需求尚未得到满足。在过去的几十年里，放疗被认为是手术和化疗的附加治疗方式。由于腹部器官的放射敏感性，高精度质子束放射治疗一直被认为是优于光子放射治疗的上级方法。为了进一步阐明联合治疗的潜力，我们采用了一种更符合生理学的3D、基于基质的细胞培养模型来评估光子和质子照射后类肿瘤形成的能力。此外，我们研究了质子和光子照射诱导的磷酸化蛋白质组学变化，以确定临床可利用的目标。在这里，我们表明，质子照射elevands更高的效率，以减少三维PDAC类瘤的形成和更大程度的磷酸化蛋白质组的改变相比，光子照射。磷酸化蛋白质组中被质子或光子独特改变的蛋白质的靶向未能引起辐射类型特异性放射增敏。然而，靶向与非同源末端连接相关的DNA修复蛋白，显示了独立于辐射类型的强大的放射增敏潜力。总之，我们的研究结果表明，质子照射在PDAC中可能比光子更有效，当与DNA修复抑制剂组合时没有额外的功效。
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.
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DOI：
10.1016/j.ijrobp.2015.06.015
发表时间：
2016-05-01
影响因子：
7
作者：
Chiblak, Sara;Tang, Zili;Abdollahi, Amir
通讯作者：
Abdollahi, Amir
影响因子：
3.1
作者：
Lühr A;von Neubeck C;Krause M;Troost EGC
通讯作者：
Troost EGC
影响因子：
2
作者：
Kageyama, Shun-ichiro;Junyan, Du;Akimoto, Tetsuo
通讯作者：
Akimoto, Tetsuo
影响因子：
9
作者：
通讯作者：
--
影响因子：
5.2
作者：
Deville, Sara Sofia;Vehlow, Anne;Cordes, Nils
通讯作者：
Cordes, Nils