Konings Katrien, Vandevoorde Charlot, Baselet Bjorn, Baatout Sarah, Moreels Marjan
Radiobiology Unit, Belgian Nuclear Research Center (SCK•CEN), Mol, Belgium.
Radiobiology, Radiation Biophysics Division, Department of Nuclear Medicine, iThemba LABS, Cape Town, South Africa.
Front Oncol. 2020 Feb 14;10:128. doi: 10.3389/fonc.2020.00128. eCollection 2020.
Radiotherapy plays a central role in the treatment of cancer patients. Over the past decades, remarkable technological progress has been made in the field of conventional radiotherapy. In addition, the use of charged particles (e.g., protons and carbon ions) makes it possible to further improve dose deposition to the tumor, while sparing the surrounding healthy tissues. Despite these improvements, radioresistance and tumor recurrence are still observed. Although the mechanisms underlying resistance to conventional radiotherapy are well-studied, scientific evidence on the impact of charged particle therapy on cancer cell radioresistance is restricted. The purpose of this review is to discuss the potential role that charged particles could play to overcome radioresistance. This review will focus on hypoxia, cancer stem cells, and specific signaling pathways of EGFR, NFκB, and Hedgehog as well as DNA damage signaling involving PARP, as mechanisms of radioresistance for which pharmacological targets have been identified. Finally, new lines of future research will be proposed, with a focus on novel molecular inhibitors that could be used in combination with charged particle therapy as a novel treatment option for radioresistant tumors.
放射治疗在癌症患者的治疗中起着核心作用。在过去几十年里，传统放射治疗领域取得了显著的技术进步。此外，使用带电粒子（如质子和碳离子）能够进一步提高肿瘤的剂量沉积，同时保护周围的健康组织。尽管有这些改进，但仍观察到放射抗性和肿瘤复发。虽然对传统放射治疗抗性的潜在机制已有充分研究，但关于带电粒子疗法对癌细胞放射抗性影响的科学证据有限。本综述的目的是讨论带电粒子在克服放射抗性方面可能发挥的潜在作用。本综述将重点关注缺氧、癌症干细胞以及表皮生长因子受体（EGFR）、核因子κB（NFκB）和刺猬因子（Hedgehog）的特定信号通路，以及涉及聚（ADP-核糖）聚合酶（PARP）的DNA损伤信号传导，这些都是已确定有药理学靶点的放射抗性机制。最后，将提出未来新的研究方向，重点是可与带电粒子疗法联合使用的新型分子抑制剂，作为放射抗性肿瘤的一种新型治疗选择。
