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A form of death by rusting: iron-driven oxidation of membrane lipids. Cancer cells in mesenchymal or drug-tolerant states depend on the GPX4 enzyme to prevent it, and the NRF2 antioxidant programme protects them further.
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
Ferroptosis is rust. Iron plus oxygen eats through the cell's membranes unless an antioxidant crew (GPX4) keeps repainting them. Cells that changed shape to dodge chemotherapy have thinner paint.
KEAP1-NRF2 is a smoke detector wired to a sprinkler system. Cancers jam the detector on, so the sprinklers run constantly and wash away every poison you throw at them.
In plain words, then the glossary entries the stage rests on. Chapter 4, Evading death and repair: To survive the damage they generate and the treatments thrown at them, cancer cells rewire death and repair.
A form of death by rusting: iron-driven oxidation of membrane lipids. Cancer cells in mesenchymal or drug-tolerant states depend on the GPX4 enzyme to prevent it, and the NRF2 antioxidant programme protects them further.
Ferroptosis & regulated cell death. Cells can die in several programmed ways. Beyond the classic apoptosis, ferroptosis kills through iron-driven fat oxidation, and drug-resistant, mesenchymal cancer cells turn out to be unusually prone to it.
KEAP1-NRF2 antioxidant pathway. KEAP1-NRF2 is the cell's antioxidant defence switch. Lung cancers often break the off-switch (KEAP1), leaving NRF2 permanently on, which detoxifies chemotherapy and radiation and makes these tumours resistant to almost everything.
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
A protein that stops cells from self-destructing. Venetoclax removes that protection and has transformed leukaemia treatment.
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
Records tied to this stage that describe resistance, evasion or tolerance. Resistance: how tumours escape each drug class lists the routes class by class.
If destroying BTK works when every inhibitor has failed, using it first might stop resistance from ever emerging.
Treatment leaves behind damaged cells that stop dividing but do not die, and they release signals that help surviving cancer cells regrow. Removing them could reduce relapse.
The cells that survive targeted therapy change shape and become unusually dependent on an antioxidant enzyme, GPX4. Hitting them in that window might stop resistance before it evolves.
Chemotherapy leaves behind senescent cells that inflame tissues and help tumours relapse. A short course of senolytic drugs afterwards might reduce relapse and long-term side effects at once.
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
Three genetic classifications of the commonest aggressive lymphoma exist and none of them yet decides anyone's treatment. The trial that would change that has not been run.
Metabolic drugs keep failing because tumours switch fuels. Measuring what a patient's tumour actually eats, with tracers and PET, could pick the right metabolic drug for the right tumour.
Small-cell lung cancer is at least four diseases under the microscope's uniform appearance. Treat each by its transcription-factor subtype.
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 4.4 of 56.