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When oxygen runs low, HIF proteins switch on a survival programme: new vessels, more glucose uptake, escape. VHL normally destroys HIF; kidney cancer loses VHL and runs the programme permanently. Belzutifan blocks HIF-2α directly.
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.
VHL is the shredder that destroys the 'we are suffocating' memo whenever there is oxygen around. Kidney cancer breaks the shredder, so the memo piles up and the cell keeps ordering new blood vessels and sugar.
In plain words, then the glossary entries the stage rests on. Chapter 5, Feeding the tumour: A tumour is a construction site that never stops.
When oxygen runs low, HIF proteins switch on a survival programme: new vessels, more glucose uptake, escape. VHL normally destroys HIF; kidney cancer loses VHL and runs the programme permanently. Belzutifan blocks HIF-2α directly.
VHL / HIF oxygen sensing. The VHL/HIF pathway is how cells sense oxygen (the 2019 Nobel Prize). VHL destroys HIF when oxygen is present. Kidney cancers lose VHL, so HIF-2α is permanently on and drives blood vessel growth and proliferation.
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 master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
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.
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.
Almost every clear-cell kidney cancer carries the CAIX protein. Image it with one radioactive antibody, then treat with the same antibody carrying a therapeutic isotope.
Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.
Cancer cells need stiff, cross-linked tissue scaffolding to settle and grow in a new organ. Blocking the enzymes that build it may stop new colonies taking hold.
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 5.4 of 56.