Tumor metastasis underlies 90% of cancer deaths. In order to evade the primary tumor and invade
other tissues, the cell undergoes dedifferentiation from epithelial to mesenchymal-like phenotype
(EMT). Tumorigenesis and EMT are associated with changes in energy requirements and with
strategies to evade normal cell death programs. There are multiple ways a cell can die. Two major
forms of cell death are apoptosis and necrosis. Historically, apoptosis was regarded as a regulated
process, while necrosis was considered accidently and uncontrollable. This view was challenged by
the discovery of several forms of regulated necrosis, such as necroptosis and ferroptosis.
Necroptosis is regulated by a kinase-signaling cascade with crucial roles for RIP kinases, ferroptosis
is an iron- and oxygen radical-dependent process and both have been reported in association with
changes in energy and redox metabolism. We hypothesize that modulations in the energy and
redox metabolism represent a potential target to specifically sensitize regulated necrosis in cancer
cells and consequently bypass apoptotic cell death resistance mechanisms these cells acquired.
We want to identify new druggable targets at the cross road of cell death, bioenergetics, redox
metabolism and EMT during cancer. Our research will lead to a better understanding of the
importance of the energy and redox metabolism for cancer development, metastasis and cell