PhD defence: Signaling networks dictating cancer cell fate: From death to adaptation through the lens of proteomics

Cancer is often described in terms of genes or metabolism, but another powerful way to understand it is as a series of life-or-death “decisions” made that cells constantly make. In healthy tissue, cells weigh signals from their environment such as stress, damage, or communication with neighboring cells to decide whether to survive, divide, or die. Cancer begins when this decision-making system becomes distorted, allowing cells to survive even when they should be eliminated.

This thesis explores how cancer cells evade these choices and how we can control their fate. Using advanced protein analysis techniques, we observe that cancer cells can block immune attacks by modifying specific proteins, effectively shielding themselves from destruction by the body’s own defense cells. We further demonstrate that tumors can suppress forms of cell death that would normally alert the immune system, revealing new vulnerabilities for therapeutic targeting. In addition, we investigate how cancer cells compete with healthy cells in organs such as the liver, reshaping their environment to gain dominance. Finally, we show how certain breast cancers develop resistance to hormone therapy by activating alternative survival pathways.

Overall, with this work we aim to highlight that cancer survival depends on adaptable protein networks. By understanding and disrupting these networks, we may be able to manipulate cell death fate as like a light switch, improving treatment outcomes.