Biophysics Department, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany.
Technische Universität Darmstadt, Institute of Condensed Matter Physics, Darmstadt, Germany.
Expert Rev Mol Med. 2022 Feb 1;24:e8. doi: 10.1017/erm.2022.2.
Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.
免疫疗法和靶向治疗现在常用于几种癌症的临床试验中，与放射治疗联合使用。虽然结果很有前景和鼓舞人心，但药物与辐射之间相互作用的分子机制在很大程度上仍不清楚。当从传统光子放疗切换到使用质子或重离子的粒子放疗时，这一点尤其重要。不同的剂量沉积模式和分子放射生物学实际上可以改变与药物的相互作用及其有效性。我们在这里将表明，虽然在低和高线性能量转移辐射暴露后主要的分子参与者是相同的，但在暴露后的信号通路中观察到显著的差异，这可能导致药物的不同效果。我们还将强调，药物给药与放射治疗之间的时间安排和分割方案是关键问题，需要紧急解决，以在粒子治疗联合治疗中取得最佳效果。
