Hill Rhianna M, Rocha Sonia, Parsons Jason L
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L7 8TX, UK.
Department of Molecular Physiology and Cell Signalling, University of Liverpool, Liverpool L69 7ZB, UK.
Cancers (Basel). 2022 Aug 26;14(17):4130. doi: 10.3390/cancers14174130.
Hypoxia is very common in most solid tumours and is a driving force for malignant progression as well as radiotherapy and chemotherapy resistance. Incidences of head and neck squamous cell carcinoma (HNSCC) have increased in the last decade and radiotherapy is a major therapeutic technique utilised in the treatment of the tumours. However, effectiveness of radiotherapy is hindered by resistance mechanisms and most notably by hypoxia, leading to poor patient prognosis of HNSCC patients. The phenomenon of hypoxia-induced radioresistance was identified nearly half a century ago, yet despite this, little progress has been made in overcoming the physical lack of oxygen. Therefore, a more detailed understanding of the molecular mechanisms of hypoxia and the underpinning radiobiological response of tumours to this phenotype is much needed. In this review, we will provide an up-to-date overview of how hypoxia alters molecular and cellular processes contributing to radioresistance, particularly in the context of HNSCC, and what strategies have and could be explored to overcome hypoxia-induced radioresistance.
缺氧在大多数实体瘤中非常普遍，是恶性进展以及放疗和化疗耐药的驱动因素。在过去十年中，头颈部鳞状细胞癌（HNSCC）的发病率有所增加，放疗是治疗这些肿瘤的主要治疗技术。然而，放疗的有效性受到耐药机制的阻碍，最显著的是缺氧，导致HNSCC患者的预后较差。缺氧诱导的放射抗性现象几乎在半个世纪前就已被发现，但尽管如此，在克服物理性缺氧方面进展甚微。因此，非常需要更详细地了解缺氧的分子机制以及肿瘤对这种表型的基础放射生物学反应。在这篇综述中，我们将提供最新概述，说明缺氧如何改变导致放射抗性的分子和细胞过程，特别是在HNSCC的背景下，以及已经探索和可以探索哪些策略来克服缺氧诱导的放射抗性。
