Exploring hypoxic biology to improve radiotherapy outcomes

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Reviews in Molecular Medicine Pub Date : 2022-04-27 DOI:10.1017/erm.2022.14
Chun Li, Lucy Wiseman, Ene Okoh, Michael J Lind, R. Roy, A. Beavis, Isabel M. Pires
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引用次数: 4

Abstract

Abstract 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.
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探索缺氧生物学改善放疗效果
摘要电离放射治疗是一种公认的、有效的癌症治疗方式,其疗效随着新技术的应用而提高。然而,患者的预后受到肿瘤生物学与放射性耐药性相关的方面的控制,并可能受到限制。由于电离辐射在肿瘤块附近的常氧组织中的作用,患者仍会忍受与治疗相关的毒性。肿瘤缺氧被认为是肿瘤微环境的关键组成部分,并被公认为会导致治疗耐药性和不良预后。在这篇综述中,我们概述了目前对缺氧介导的放疗耐药性的理解,然后探索靶向肿瘤缺氧进行放疗增敏,以改善治疗结果并增加治疗窗口。这包括增加实体瘤的氧气供应,使用缺氧激活的前药,靶向缺氧调节或相关的信号通路,以及使用高LET放射治疗模式。最终,靶向低氧放射生物学与精确的放射治疗递送模式和建模相结合,应该与改善患者预后有关。
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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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