Radiation-induced Adaptive Response: New Potential for Cancer Treatment.
Radiation-induced Adaptive Response: New Potential for Cancer Treatment.
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辐射诱导的适应性反应：癌症治疗的新潜力。
DOI：
10.1158/1078-0432.ccr-20-0572
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发表时间：
2020-11-15
期刊：
影响因子：
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通讯作者：
Aryankalayil MJ
中科院分区：
文献类型：
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作者：
Coleman CN;Eke I;Makinde AY;Chopra S;Demaria S;Formenti SC;Martello S;Bylicky M;Mitchell JB;Aryankalayil MJ
放射治疗（RT）是非常有效的，因为它能够物理聚焦治疗靶向肿瘤，同时保留正常组织，并能够与全身治疗相结合。这种全身性治疗可以在RT之前用作辅助或诱导治疗，在RT期间用作辐射“增敏剂”，或在RT之后用作联合模式治疗的一部分。作为使用辐射作为“聚焦生物学”的独特概念的一部分，我们研究了肿瘤和正常组织如何适应临床相关的多部分（MF）和单剂量（SD）辐射，以观察这些适应是否可以诱导对可用药物或免疫增强的细胞杀伤的敏感性。我们发现了一种适应发生在MF之后，此外，我们确定了RT停止后2个月整合素表达的诱导性变化，这些变化在MF和MF之间不同。（1戈伊× 10）和SD（10戈伊），与RT前相比仍然是可靶向的。适应性反映在不同的“组学”研究中，因此可能的分子靶点的范围不仅广泛，而且依赖于时间、剂量和时间表。尽管关于辐射适应性反应仍有许多问题有待研究，但除了物理剂量外，辐射的特征应在于其分子扰动。考虑到适应性效应，应设计一个量身定制的放射治疗计划，考虑到特定的分子变化，作为精确的多模态癌症治疗的一部分。
Radiation therapy (RT) is highly effective due to its ability to physically focus the treatment to target the tumor while sparing normal tissue and its ability to be combined with systemic therapy. This systemic therapy can be utilized before RT as an adjuvant or induction treatment, during RT as a radiation “sensitizer,” or following RT as a part of combined modality therapy. As part of a unique concept of using radiation as “focused biology” we investigated how tumors and normal tissues adapt to clinically relevant multi-fraction (MF) and single-dose (SD) radiation to observe whether the adaptations can induce susceptibility to cell killing by available drugs or by immune enhancement. We identified an adaptation occurring after MF (3 × 2 Gy) that induced cell killing when AKT-mTOR inhibitors were delivered following cessation of RT. Additionally, we identified inducible changes in integrin expression 2 months following cessation of RT that differ between MF (1 Gy x 10) and SD (10 Gy) that remain targetable compared to pre-RT. Adaptation is reflected across different “omics” studies, and thus the range of possible molecular targets is not only broad but also time, dose, and schedule dependent. While much remains to be studied about the radiation adaptive response, radiation should be characterized by its molecular perturbations in addition to physical dose. Consideration of the adaptive effects should result in the design of a tailored radiotherapy treatment plan that accounts for specific molecular changes to be targeted as part of precision multi-modality cancer treatment.