BCRB 2018

19/09/2018

Targeting hypoxia – holy grail of radiotherapy?

• Hypoxia targeting has come a long way, from increasing oxygen supply and enhancing perfusion, to inhibitors of specific signaling or metabolic pathways • Tumor hypoxia represents a highly dynamic condition, distributed heterogeneously in tumors and changing over time • The concept of acute vs chronic hypoxia is clearly an oversimplification of a complex condition • The comeback of large doses/fx or even single doses also needs consideration of adding relatively non-toxic hypoxic sensitizers like nimorazole: “back to the future”

Patient selection

• Endogenous biomarkers for hypoxia

Swartz JE et al Cancer Med 2015

Low EMH expression

(HIF-1a, CA-IX, GLUT-1, OPN) - Better prognosis (overall survival)

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Favors low expression Favors high expression