BCRB 2018

Summary w Mechanisms responsible for tumor hypoxia – chronic and acute – Supply, demand, tolerance w Hypoxia is heterogeneous – amount, spatial, severity, time w Hypoxia promotes treatment resistance

– Radioresistance due to lack of ‘fixation’ of DNA damage – Chemoresistance due to cell cycle arrest ++

w Hypoxia promotes malignancy

– Tumors become hypoxia tolerant (selection for p53 mutations) – Hypoxia alters cellular function through transcription, translation and protein activity