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Every cause of DNA damage leaves its own fingerprint. Sunlight, tobacco, a missing repair enzyme, even a gut bacterium, each write a recognisable pattern into the genome. Those patterns say what caused a cancer and which repair crews it lacks.
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.
Footprints in snow. A fox, a dog and a child each leave a distinct print; you can tell who crossed the garden without having seen them. Cancer genomes are snowfields, and each mutagen and each broken repair crew leaves its own print.
In plain words, then the glossary entries the stage rests on. Chapter 2, How a cell becomes cancer: Cancer is evolution inside a body.
Every cause of DNA damage leaves its own fingerprint. Sunlight, tobacco, a missing repair enzyme, even a gut bacterium, each write a recognisable pattern into the genome. Those patterns say what caused a cancer and which repair crews it lacks.
Mutagenesis & mutational signatures. Every cause of DNA damage leaves its own fingerprint in the genome: sunlight, tobacco, a faulty repair enzyme, a gut bacterium. Reading these fingerprints tells you what caused a cancer and which repair crews it is missing, which in turn predicts which drugs will work.
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.
DNA repair genes. Inheriting a broken copy raises breast and ovarian cancer risk, but tumours that lose them become uniquely vulnerable to PARP inhibitors and platinum.
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.
Some tumours change fast and escape drugs quickly; others are stable. A single validated score for how evolvable a tumour is would tell doctors how aggressively to combine treatments.
Subsets of lung, bladder and breast cancers carry raised APOBEC enzyme activity that keeps generating new mutations, feeding resistance. Blocking APOBEC3 alongside a targeted drug aims not to kill cells but to slow the rate at which resistant variants arise; the inhibitors are still in discovery.
Under treatment stress, cancer cells switch on sloppy DNA copying that generates the mutations they need to survive. Blocking that machinery could stop resistance being invented.
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.
For some cancers, drugs and radiotherapy can now cure without removing the organ, sparing patients a stoma, a lost voice or a removed bladder. A dedicated programme would run the trials to prove where this is safe.
Anyone with ovarian, pancreatic, metastatic prostate or mismatch-repair-deficient colorectal cancer should be tested for inherited mutations, yet testing rates fall well short. Making it an automatic, opt-out laboratory step triggered by pathology, as reflex mismatch-repair testing already is, would close the gap.
Scotland and Wales put a floor under the price of alcohol. Deaths from liver disease have already fallen. Cancer takes longer to show, so someone has to keep measuring for a decade.
Aspirin roughly halves bowel cancer in Lynch syndrome, and a dose trial is defining how little is needed. Most carriers are still not prescribed it; the task is to fix prescribing.
Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.
For each cancer type, agree the set of stains and tests that are always needed, and have the lab run them automatically on diagnosis rather than waiting for someone to ask.
People with Lynch syndrome have a very high lifetime cancer risk from a predictable set of mutations. Vaccinate them against those shared mutations before cancer appears.
Lynch syndrome tumours share predictable mutations the immune system can target. A vaccine in early trials could be tested to see if it prevents polyps and cancers in carriers.
Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.
Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.
8 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
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 2.1 of 56.