Epithelial-mesenchymal transition and H 2 O 2 signaling - a driver of disease progression and a vulnerability in cancers.

Mutation-selective drugs constitute a great advancement in personalized anticancer treatment with increased quality of life and overall survival in cancers. However, the high adaptability and evasiveness of cancers can lead to disease progression and the development of drug resistance, which cause recurrence and metastasis. A common characteristic in advanced neoplastic cancers is the epithelial-mesenchymal transition (EMT) which is strongly interconnected with H 2 O 2 signaling, increased motility and invasiveness. H 2 O 2 relays its signal through the installation of oxidative posttranslational modifications on cysteines. The increased H 2 O 2 levels that are associated with an EMT confer a heightened sensitivity towards the induction of ferroptosis as a recently discovered vulnerability.