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Cancers run a few genes at deafening volume from super-enhancers, and MYC is the master amplifier. The machinery is shared with normal cells, but tumours depend on it more, and hormone receptors are the oldest transcription drugs.
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 conductor who can make every section of the orchestra play louder at once. You cannot take away the baton, so drugs try to silence the score (transcription), tire the conductor (degradation), or exploit the fact that a full-volume orchestra cannot afford a single missing player.
A concert where a few songs are played at deafening volume through rented amplifiers. Cutting the mains for a moment (BET, CDK7/9 inhibitors) silences the loudest songs first because their sound decays fastest, while the quieter household appliances keep humming.
Splicing is film editing. The raw footage (pre-mRNA) is cut into a final movie. Cancer's editor makes odd cuts: some create villains (AR-V7), some create scenes no one has seen before (neoantigens), and the editing room itself becomes a place where the cancer can be attacked.
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.
Cancers run a few genes at deafening volume from super-enhancers, and MYC is the master amplifier. The machinery is shared with normal cells, but tumours depend on it more, and hormone receptors are the oldest transcription drugs.
MYC. MYC is the most commonly amplified cancer gene, a master switch that turns on thousands of growth genes. It has no pocket for a conventional drug, so it remained 'undruggable' for 40 years; the first direct MYC drugs finally entered trials in the 2020s.
Transcriptional machinery & addiction. Cancer cells run a few genes (MYC, their lineage factors, their fusion oncogenes) at extreme volume from giant control regions called super-enhancers. The amplifiers, BRD4, CDK7, CDK9 and Mediator, are the same in every cell, but cancers are unusually dependent on them, and that dependence is druggable.
RNA splicing. Genes are cut and pasted into messages before they are used. Blood cancers often carry mutations in the splicing machinery, and the errors create abnormal proteins that could serve as targets or immune flags.
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 prostate cancer, attacked by castration and by pills that block the receptor.
The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.
A scaffold protein that certain leukaemias need to keep their genes switched on; the first drug against it was approved in 2024.
The fused gene that defines Ewing sarcoma: an aberrant transcription factor that has resisted 30 years of drug design.
CD47 is the 'don't eat me' signal: it binds SIRP-alpha on macrophages to stop them engulfing the cell, and over 90% of AML blasts and large B-cell lymphoma cells display it. Blocking it should let macrophages eat tumour cells, but red cells carry CD47 too, so anaemia is built in, and the lead antibody magrolimab was dropped after failed trials.
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.
Giving men with castration-resistant prostate cancer large doses of the hormone the treatment has spent years removing makes a third of them respond, and makes half of them respond again to the drug that had stopped working. It has never been taken to a definitive trial, partly because the endpoint that shows the benefit is not the one trials usually use.
In advanced prostate cancer the AR-V7 splice variant of the androgen receptor lacks the ligand-binding domain that enzalutamide and abiraterone act on, and its presence predicts resistance. A degrader or N-terminal binder that removes the whole protein, variants included, would still work; AR-V7 is already measurable in circulating tumour cells.
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.
In a minority of men, prostate cancer escapes hormone drugs by becoming a different kind of cell that no longer needs the androgen receptor. By the time a biopsy shows it, the treatment options are almost gone. The genetic changes that allow the switch are detectable years earlier, and nobody is looking for them.
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.
Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until there is a real drug candidate, then competing on the final product.
MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. The first direct MYC blockers are in trials; the question is whether there is a therapeutic window.
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.
Infant leukaemia is driven almost entirely by KMT2A fusions, which menin inhibitors were built to attack. Add them to the new blinatumomab-containing backbone.
Mutations in the RNA splicing genes SF3B1, SRSF2 and U2AF1 produce the same mis-spliced proteins in patient after patient with MDS, CLL or uveal melanoma. If fragments of those proteins are displayed on common HLA molecules and seen by T cells, one off-the-shelf vaccine or TCR-T therapy could serve every SF3B1-mutant patient instead of being built per person.
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 3.6 of 56.