Hypoxia Re-Oxygenation Modelling Using Cancer Cells Expressing Cell Cycle and Cell Death Probes to Understand the Dynamics of Resistance Mechanisms.

We have shown that the hypoxic exposures alter the cells' ability to undergo apoptosis dynamically after its recovery under normoxia. Initially, the cells adapt to hypoxia through mitophagy dependent manner that alters its cell cycle progression both in normoxia and hypoxia. Despite adaptive mitophagy, hypoxic cells remain sensitive to re-oxygenation and also to cancer drugs owing to the oxidation damage to organelles. However, rare cells survive during these two events progresses towards expansion with a highly variable mitochondrial density that governs differing functional traits of cell cycle, cell death response, ability to invade and migrate. This functional heterogeneity appears to play a key role in temporally regulated tumor resistance and recurrences.