Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.853568
Keywords
tumor hypoxia; oxygen; imaging; biomarker; cancer; predictive marker; therapy; theranostics
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Hypoxia is a common feature of solid tumors and plays a role in tumor progression and resistance to therapy. Despite various approaches to target hypoxia, their translation into clinical practice has been disappointing. Companion diagnostics may help in matching patients with specific interventions.
Hypoxia is a common feature of solid tumors that contributes to angiogenesis, invasiveness, metastasis, altered metabolism and genomic instability. As hypoxia is a major actor in tumor progression and resistance to radiotherapy, chemotherapy and immunotherapy, multiple approaches have emerged to target tumor hypoxia. It includes among others pharmacological interventions designed to alleviate tumor hypoxia at the time of radiation therapy, prodrugs that are selectively activated in hypoxic cells or inhibitors of molecular targets involved in hypoxic cell survival (i.e., hypoxia inducible factors HIFs, PI3K/AKT/mTOR pathway, unfolded protein response). While numerous strategies were successful in pre-clinical models, their translation in the clinical practice has been disappointing so far. This therapeutic failure often results from the absence of appropriate stratification of patients that could benefit from targeted interventions. Companion diagnostics may help at different levels of the research and development, and in matching a patient to a specific intervention targeting hypoxia. In this review, we discuss the relative merits of the existing hypoxia biomarkers, their current status and the challenges for their future validation as companion diagnostics adapted to the nature of the intervention.
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