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Each year, about one in every 100,000 children develops a new neuroblastoma, usually in the first year of life
An important regulator that determines the direction of disease development is the cancer gene MYCN
These are the questions asked by a team of scientists led by Frank Westermann, Andreas Trumpp, DKFZ and HI-STEM gGmbH from the Hopp Children's Cancer Center (KiTZ) and the German Cancer Research Center (DKFZ) in Heidelberg and Thomas Höfer from the DKFZ
At the same time, cancer cells need cysteine to protect themselves from naturally occurring toxic peroxides, which are conditionally produced by cancer cells' highly active metabolism
However, it is these adaptive processes that sensitize neuroblastoma cells
Scientists deliberately turned off the faucet to the tumor: They blocked cysteine uptake, cysteine synthesis, and shut down a key enzyme that normally prevents cancer cells from poisoning themselves with peroxides
Hamed Alborzinia emphasizes: "Ferroptosis cell death was only discovered a few years ago, and the results now show for the first time that this process can be controlled, not only in cell culture, but also in cancer-bearing mice, by inducing Ferroptosis to kill highly aggressive human neuroblastoma cells
This finding also provides a possible explanation for why neuroblastomas with moderate MYCN activity in infants and young children disappear in some cases: "The cells essentially take up less cysteine in the first few years of life
For high-risk patients with high MYCN activity, the study provides the first insight into how the balance between cysteine uptake, production and consumption may be disturbed so that these cells also begin to self-destruct
The study was published in the journal Nature Cancer
