Bhattacharya Poushali, Shetake Neena G, Pandey Badri N, Kumar Amit
a Radiation Signaling and Cancer Biology Section, Radiation Biology and Health Sciences Division , Bhabha Atomic Research Centre , Mumbai , India.
Int J Radiat Biol. 2018 Jul;94(7):628-644. doi: 10.1080/09553002.2018.1478160. Epub 2018 Jun 19.
One of the most important implications of 'Radiation Biology' research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer. Moreover, an early successful clinical trial using RTK-antagonist (cetuximab) to improve tumor radiosensitivity has led to an advancement in this field of research. However, a comprehensive review integrating these findings of various oncogenic RTKs, from basic radiobiology-to-radiotherapy clinical trials, is lacking in literature. Therefore, the present review analyses relevant in-vitro, in-vivo, preclinical/clinical studies and postulates the concept of 'Radiation Biology of RTKs in Cancer'.
The present review elucidates the effect of IR on various oncogenic RTKs and their mechanisms, downstream signaling, intracellular translocations, their role in the repair of radiation-induced DNA damage and post-irradiation survival. Based on the knowledge derived from RTK biology and the analysis of relevant clinical trials, this review attempts to identify radiobiological considerations, which could be implemented in future trials, combining radiotherapy with RTK-antagonist. Additionally, we identify the radiosensitizing potential of recently developed RTK-targeted nanoformulations. This review would probably change the Radiation Oncologist's view for translation of tumor-specific radiosensitization in clinic.
“放射生物学”研究的最重要意义之一是在将副作用降至最低的情况下改善癌症放疗。在这方面，化疗与放疗相结合已显著提高了多种癌症的肿瘤控制率和总生存率。然而，由于化疗缺乏特异性，这是以显著的正常组织毒性为代价实现的。已发现膜定位受体酪氨酸激酶（RTK）在癌症的各种特征中起驱动作用。此外，一项早期成功的使用RTK拮抗剂（西妥昔单抗）提高肿瘤放射敏感性的临床试验推动了该研究领域的发展。然而，文献中缺乏一篇综合综述来整合从基础放射生物学到放疗临床试验的各种致癌RTK的这些发现。因此，本综述分析了相关的体外、体内、临床前/临床研究，并提出了“癌症中RTK的放射生物学”概念。
本综述阐明了电离辐射（IR）对各种致癌RTK的影响及其机制、下游信号传导、细胞内易位、它们在辐射诱导的DNA损伤修复和照射后存活中的作用。基于从RTK生物学获得的知识以及对相关临床试验的分析，本综述试图确定可在未来将放疗与RTK拮抗剂相结合的试验中实施的放射生物学考量因素。此外，我们确定了最近开发的RTK靶向纳米制剂的放射增敏潜力。本综述可能会改变放射肿瘤学家对临床肿瘤特异性放射增敏转化的看法。
