PhD defence: Mitochondria taking center stage in therapy-induced senescence - Mechanisms and therapeutic implications for cancer

PLEASE NOTE: If a candidate gives a layman's talk, the livestream will start fifteen minutes earlier.

Cancer treatments aim to stop tumors from growing, but cancer cells do not always die in response. Instead, many enter a state called therapy-induced senescence, in which cells stop dividing but remain alive. At first, this can be beneficial because it slows or halts tumor growth. Over time, however, these surviving cells can become harmful by releasing signals that promote inflammation and increase the risk that cancer returns.

This thesis shows that mitochondria, often known as the cell’s power plants, play a much larger role in this process than previously thought. Rather than being parts of the cell that are simply damaged by treatment, mitochondria actively influence how cancer cells respond. Disrupting mitochondrial function alone can be enough to push cancer cells into senescence.

The work suggests that changes in how mitochondria produce energy, respond to stress, and make their own proteins all contribute to maintaining this senescent state. Importantly, the condition of mitochondria also affects whether senescent cancer cells can later be removed by drugs designed to clear them. Some senescent cancer cells are easier to eliminate than others, and mitochondrial differences help explain this variability.

By developing new ways to study proteins made inside mitochondria, this thesis also identifies small mitochondrial proteins that may influence whether senescence is maintained or reversed.

Together, these findings highlight mitochondrial regulation as a key determinant of therapy-induced senescence and suggest that deeper insight into mitochondrial processes may improve how senescence is exploited or targeted in cancer treatment.