Tumour hypoxia in clinical oncology: imaging, therapeutic strategies, and translational challenges.

Hypoxia, a defining feature of many solid tumours, arises from rapid cellular proliferation, abnormal tumour stroma, and aberrant vasculature. Reduced oxygen availability contributes to several cancer hallmarks, including sustained proliferative signalling, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. Consistent with these biological effects, tumour hypoxia is associated with poorer prognosis across multiple cancer types, irrespective of treatment modality. Consequently, the characterisation and therapeutic leverage of hypoxic tumour status have been key areas of clinical investigation over the past three decades. However, despite extensive research, no method for routine clinical stratification of tumours by hypoxic status has been widely adopted, and hypoxia-targeted or hypoxia-alleviating treatments remain limited in clinical use. This review summarises the clinical progress and ongoing challenges in hypoxia imaging and therapeutic intervention. It focuses on strategies designed to enhance oxygen delivery, exploit hypoxic tumour environments through hypoxia-activated prodrugs, or modify tumour oxygen consumption. By these approaches under clinical evaluation, this review aims to identify key barriers to the integration of hypoxia-focused intervention and highlight the volume and diversity of hypoxia targeted treatments that are pending clinical translation.