Hypoxia and Tumour Microenvironment Lab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK.
Queen's Centre for Oncology and Haematology, Castle Hill Hospital, Castle Rd, Cottingham HU16 5JQ, UK.
Expert Rev Mol Med. 2022 Apr 27;24:e21. doi: 10.1017/erm.2022.14.
Ionising radiotherapy is a well-established, effective cancer treatment modality, whose efficacy has improved with the application of newer technological modalities. However, patient outcomes are governed and potentially limited by aspects of tumour biology that are associated with radioresistance. Patients also still endure treatment-associated toxicities owed to the action of ionising radiation in normoxic tissue adjacent to the tumour mass. Tumour hypoxia is recognised as a key component of the tumour microenvironment and is well established as leading to therapy resistance and poor prognosis. In this review, we outline the current understanding of hypoxia-mediated radiotherapy resistance, before exploring targeting tumour hypoxia for radiotherapy sensitisation to improve treatment outcomes and increase the therapeutic window. This includes increasing oxygen availability in solid tumours, the use of hypoxia-activated prodrugs, targeting of hypoxia-regulated or associated signalling pathways, as well as the use of high-LET radiotherapy modalities. Ultimately, targeting hypoxic radiobiology combined with precise radiotherapy delivery modalities and modelling should be associated with improvement to patient outcomes.
电离放射疗法是一种成熟有效的癌症治疗方法，随着新技术模式的应用，其疗效得到了提高。然而，肿瘤生物学方面的一些因素与放射抵抗有关，这些因素可能会影响患者的预后。由于肿瘤周围正常组织中存在电离辐射，患者仍会遭受与治疗相关的毒性。肿瘤缺氧被认为是肿瘤微环境的一个关键组成部分，它导致治疗抵抗和预后不良已得到充分证实。在这篇综述中，我们概述了目前对缺氧介导的放射抵抗的理解，然后探讨了针对肿瘤缺氧以提高放射治疗敏感性，从而改善治疗效果和扩大治疗窗口的方法。这包括增加实体瘤中的氧气供应、使用缺氧激活前药、靶向缺氧调节或相关信号通路，以及使用高传能线密度放射治疗模式。最终，靶向缺氧放射生物学并结合精确的放射治疗输送模式和建模，应该可以改善患者的预后。
