Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Rm 208C Traylor Building, Baltimore, MD, 21205, USA.
Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cancer Metastasis Rev. 2019 Jun;38(1-2):51-64. doi: 10.1007/s10555-019-09788-3.
Hypoxia in cancers has evoked significant interest since 1955 when Thomlinson and Gray postulated the presence of hypoxia in human lung cancers, based on the observation of necrosis occurring at the diffusion limit of oxygen from the nearest blood vessel, and identified the implication of these observations for radiation therapy. Coupled with discoveries in 1953 by Gray and others that anoxic cells were resistant to radiation damage, these observations have led to an entire field of research focused on exploiting oxygenation and hypoxia to improve the outcome of radiation therapy. Almost 65 years later, tumor heterogeneity of nearly every parameter measured including tumor oxygenation, and the dynamic landscape of cancers and their microenvironments are clearly evident, providing a strong rationale for cancer personalized medicine. Since hypoxia is a major cause of extracellular acidosis in tumors, here, we have focused on the applications of imaging to understand the effects of hypoxia in tumors and to target hypoxia in theranostic strategies. Molecular and functional imaging have critically important roles to play in personalized medicine through the detection of hypoxia, both spatially and temporally, and by providing new understanding of the role of hypoxia in cancer aggressiveness. With the discovery of the hypoxia-inducible factor (HIF), the intervening years have also seen significant progress in understanding the transcriptional regulation of hypoxia-induced genes. These advances have provided the ability to silence HIF and understand the associated molecular and functional consequences to expand our understanding of hypoxia and its role in cancer aggressiveness. Most recently, the development of hypoxia-based theranostic strategies that combine detection and therapy are further establishing imaging-based treatment strategies for precision medicine of cancer.
自 1955 年 Thomlinson 和 Gray 基于从最近的血管扩散氧气的极限处观察到的坏死现象，推测人肺癌存在缺氧，并指出这些观察结果对放射治疗的意义以来，癌症缺氧一直引起了广泛关注。再加上 Gray 等人在 1953 年发现乏氧细胞对辐射损伤有抗性，这些观察结果催生了一个专注于利用氧合和缺氧来改善放射治疗效果的研究领域。近 65 年后，几乎所有参数的肿瘤异质性都得到了明确的证实，包括肿瘤氧合作用，以及癌症及其微环境的动态景观，为癌症个体化医学提供了强有力的依据。由于缺氧是肿瘤细胞外酸中毒的主要原因，在这里，我们重点关注成像应用，以了解肿瘤缺氧的影响，并将其作为治疗策略中的靶向治疗。分子和功能成像在个体化医学中具有至关重要的作用，通过检测缺氧的时空分布，并通过提供对缺氧在癌症侵袭性中的作用的新认识，发挥着重要作用。随着缺氧诱导因子 (HIF) 的发现，近年来在理解缺氧诱导基因的转录调控方面也取得了重大进展。这些进展提供了沉默 HIF 的能力，并理解相关的分子和功能后果，从而扩展了我们对缺氧及其在癌症侵袭性中的作用的理解。最近，基于缺氧的治疗策略的发展，将检测和治疗相结合，进一步为癌症精准医学建立了基于成像的治疗策略。
