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All cells must continuously manage reactivity – the chemistry that sustains life but also threatens it. Endogenous aldehydes such as formaldehyde are unavoidable byproducts of essential metabolism that challenge genome integrity, while uncontrolled lipid peroxidation can lead to ferroptotic cell death when antioxidant capacity becomes compromised. Both stresses are mainly handled by the same nucleophilic molecule: glutathione, creating a fundamental trade-off that must be resolved. In this lecture, I will discuss how cancer cells rewire their nucleophilic metabolism to navigate this conflict, prioritizing aldehyde detoxification or ferroptosis resistance according to their oncogenic landscape.
