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Unwanted proteins are tagged with ubiquitin and fed into a shredder. Myeloma dies when the shredder jams; and the newest drugs forge the tags so that a cancer destroys its own oncoproteins.
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.
A recycling plant with barcode stickers (ubiquitin) and a shredder (proteasome). Myeloma is a paper mill that produces so much waste it dies when the shredder stops (bortezomib). PROTACs and glues are forged stickers that get the plant to shred the cancer's own machinery.
In plain words, then the glossary entries the stage rests on. Chapter 3, Replication and growth machinery: Cancer cells use the same engine as normal cells, only stuck at full throttle.
Unwanted proteins are tagged with ubiquitin and fed into a shredder. Myeloma dies when the shredder jams; and the newest drugs forge the tags so that a cancer destroys its own oncoproteins.
Ubiquitin-proteasome system & protein homeostasis. Cells tag unwanted proteins with a small marker called ubiquitin and feed them into a shredder, the proteasome. Myeloma cells, which make antibody in bulk, die if the shredder jams; and the newest drugs hijack the tagging machinery to make a cancer destroy its own oncoproteins.
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.
The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.
The signalling enzyme that B-cell cancers use to survive. Blocking it turned chronic lymphocytic leukaemia into a disease controlled by a daily pill.
MDM2 is the protein that degrades p53; blocking it reactivates p53 in tumours where the gene is intact, especially the liposarcomas that carry extra copies of MDM2.
A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
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.
Resistance mutations often exist in a tiny fraction of cells before treatment starts. Error-corrected sequencing that detects variants below 0.01 percent allele fraction could find them at diagnosis and prompt a mechanism-matched combination from day one.
Resistance often arrives as the same few mutations. Teaching the immune system to recognise them in advance could remove the escaping cells while they are still rare.
Biomarkers, tests and assays in the corpus that read this stage in a patient.
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.
Several treatments now work without chemotherapy, but most are given until the disease comes back. Giving them for a fixed time and stopping is the version patients would choose.
A 5 mg tamoxifen dose halves breast cancer recurrence after precancer with far fewer side effects than the full dose. Almost nobody is prescribed it. Change who can prescribe.
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.
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 3.8 of 56.