Recent advances in the biology of tumour hypoxia with relevance to diagnostic practice and tissue‐based research

Abstract

In this review article, we examine the importance of low levels of oxygen (hypoxia) in cancer biology. We provide a brief description of how mammalian cells sense oxygen. The hypoxia-inducible factor (HIF) pathway is currently the best characterised oxygen-sensing system, but recent work has revealed that mammals also use an oxygen-sensing system found in plants to regulate the abundance of some proteins and peptides with an amino-terminal cysteine residue. We discuss how the HIF pathway is affected during the growth of solid tumours, which develop in microenvironments with gradients of oxygen availability. We then introduce the concept of 'pseudohypoxia', a state of constitutive, oxygen-independent HIF system activation that occurs due to oncogenic stimulation in a number of specific tumour types that are of immediate relevance to diagnostic histopathologists. We provide an overview of the different methods of quantifying tumour hypoxia, emphasising the importance of pre-analytic factors in interpreting the results of tissue-based studies. Finally, we review recent approaches to targeting hypoxia/HIF system activation for therapeutic benefit, the application of which may require knowledge of which hypoxia signalling components are being utilised by a given tumour.

Selection of metastasis competent subclones in the tumour interior: TRACERx renal

“…In addition hypoxia has a wellestablished role as a microenvironmental factor promoting metastasis 19 . Of separate note, ccRCC is additionally uniquely characterised by oxygen-independent so called "pseudohypoxia" as a universal feature of the disease due to VHL inactivation 20 . Clinically, necrosis is associated with ischemia, either as a chronic process resulting in gradual tissue damage, or as an acute event such as infarction related to arterial or venous thrombosis.…”

Oxygen sensing; a stunningly elegant molecular machinery highjacked in cancer

“…How do we accurately measure hypoxia? The interested reader is referred to the excellent review by Macklin et al (60).…”

Association of JMJD2B and Hypoxia-Inducible Factor 1 Expressions with Poor Prognosis in Osteosarcoma

“…HIF1 is overexpressed in a variety of solid tumors [ 13 ]. Moreover, our previous study indicated that HIF1 was overexpressed and possibly mediated hypoxia-induced autophagic activation in human OS tissues [ 14 ].…”