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A tumour is a population, not a clone. Subclones compete, therapy selects the fittest, and relapse is usually a minority that was there all along. Chromosome shuffling speeds evolution; blood tests can follow it in real time.
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.
Clonal evolution is like weeding a field with one herbicide year after year: the field fills with the one weed that shrugs it off. Rotating herbicides and leaving some susceptible weeds to crowd out the resistant ones is the evolutionary alternative.
Weeds in the blood's seed bank. Harmless individually, they spread with age and after chemical sprays, some turn into leukaemia, and their DNA litters the blood, so a test for tumour DNA can mistake weeds for cancer.
Chromosomal instability is a library that reshuffles and duplicates random shelves every night. Most rearrangements are useless, some ruin the building, but occasionally one yields a book the librarian needs to survive a new rule, and the mess itself keeps the fire alarms twitching.
In plain words, then the glossary entries the stage rests on. Chapter 2, How a cell becomes cancer: Cancer is evolution inside a body.
A tumour is a population, not a clone. Subclones compete, therapy selects the fittest, and relapse is usually a minority that was there all along. Chromosome shuffling speeds evolution; blood tests can follow it in real time.
Clonal evolution & minimal residual disease. A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy.
Clonal haematopoiesis (CHIP). As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA.
Chromosomal instability & aneuploidy. Most cancers have the wrong number of chromosomes and keep shuffling them at every division. This chaos fuels evolution and drug resistance, but it also stresses the cell and can trigger immune alarms, a double edge that researchers are trying to exploit.
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.
TP53 is the 'guardian of the genome', broken in half of all cancers. Fixing it directly has so far defeated every attempt, so drugs exploit what its loss makes cancers depend on.
A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
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.
The first drug against the KRAS protein nearly doubled survival in pancreatic cancer in 2026, but on its own it holds the disease for months, not years. Trials are now testing it in combination with a second RAS drug and with chemotherapy, and earlier in the disease; the open questions are which combination, in which order, and what works when the tumour escapes.
Instead of hitting a tumour with the maximum dose until it stops working, adjust the dose to keep the tumour small and let drug-sensitive cells suppress resistant ones. Test this properly across several cancers.
When patients who agreed in advance die of cancer, sampling every tumour within hours reveals how the disease evolved and escaped every drug. Few hospitals can do this today.
After surgery or curative treatment, everyone gets regular blood tests for leftover cancer DNA, and the pooled results power forecasts of who will relapse and trials of acting early.
Some people have only a few sites of spread and can be treated at each one; others have further deposits not yet visible, and counting lesions cannot tell them apart. A signature built from tumour DNA levels, microRNA classifiers and clonal diversity across lesions would define the biology and spare futile ablation.
Rather than giving the same dose until the cancer grows, measure tumour DNA in blood every few weeks and let a validated algorithm raise, lower, pause or switch drugs to keep the cancer suppressed for longer.
When a scan shows most tumours shrinking but one growing, that odd lesion holds the escape mechanism. Sampling it, and treating it locally, should be routine.
After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.
Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.
Track FGFR2 resistance mutations in blood and switch to the next-generation inhibitor that still covers them, before the scan shows progression.
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.
Blood tests can now find leftover cancer months before scans, but most patients who test positive have nothing to enrol in. One standing trial per country would fix that.
Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives.
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.
A blood test after surgery already lets stage II colon cancer patients skip chemotherapy safely. The same test in stage III would spare far more people, and the unproven half, giving more chemotherapy to those who test positive, has so far changed nothing.
A Japanese trial found vitamin D supplements did not help everyone after digestive cancer surgery, but appeared to help a subgroup identified by a tumour marker. That subgroup deserves its own trial.
Blood tests can already detect tumour DNA. Reporting which sub-populations of the tumour are growing or shrinking, cycle by cycle, would turn the test into an evolution monitor.
After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.
Between diagnosis and surgery there are usually a few weeks. Giving a new drug in that window and comparing the tumour before and after surgery shows whether it hits its target in real people, quickly and cheaply.
Once a year, send the same blinded blood samples to every company selling a tumour-DNA test and publish how each performed.
Trials often measure a stand-in for survival, such as time until the cancer grows on scans. An independent body would test, for each cancer and treatment type, whether the stand-in actually predicts survival, and publish the answer.
93 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 2.3 of 56.