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Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation. They go quiet, stop dividing, and wait; true resistance often grows out of them. They are hard to kill because they do so little, but they have weaknesses of their own.
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.
Bears in hibernation while the forest burns. Poison meant for grazing animals does nothing to a sleeping bear; but a hibernating bear cannot run, so a hunter who knows where the den is (GPX4, BCL-XL) can strike.
Ferroptosis is rust. Iron plus oxygen eats through the cell's membranes unless an antioxidant crew (GPX4) keeps repainting them. Cells that changed shape to dodge chemotherapy have thinner paint.
In plain words, then the glossary entries the stage rests on. Chapter 9, Why treatments fail: Every cancer drug eventually meets resistance.
Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation. They go quiet, stop dividing, and wait; true resistance often grows out of them. They are hard to kill because they do so little, but they have weaknesses of their own.
Drug-tolerant persister cells. Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.
Ferroptosis & regulated cell death. Cells can die in several programmed ways. Beyond the classic apoptosis, ferroptosis kills through iron-driven fat oxidation, and drug-resistant, mesenchymal cancer cells turn out to be unusually prone to it.
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 growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
EZH2 is an enzyme that silences genes. The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
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.
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.
If most tumours escape a drug by the same back-up route, blocking that route from the start may prevent resistance rather than chase it.
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.
If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it.
Because cervical tumours carry viral DNA that normal cells do not, a blood test for HPV DNA is a near-perfect tumour marker for tracking response and relapse.
Instead of trying to kill every hidden cancer cell after surgery, keep them dormant for life with low-toxicity drugs, the way extended hormone therapy already does in breast cancer.
Individualised mRNA cancer vaccines take weeks to manufacture and work best against minimal residual disease. Making the vaccine at surgery and giving it only when a blood tumour DNA test turns positive matches both facts and concentrates the cost on the minority who will relapse.
Fluid taken from the lower back contains DNA from brain tumours. Testing it can diagnose, monitor and detect resistance without brain surgery.
Dormant cancer cells hide in bone marrow. A lab-built model of that hiding place would let us watch them sleep and wake, and test drugs on them.
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.
Pack-year rules miss people who get lung cancer without heavy smoking, including East Asian women who never smoked, as Taiwan's TALENT study showed. Eligibility by a validated risk model with a set threshold, plus a never-smoker arm where family history matters, would find more cancers per scan.
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.
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.
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.
Sleeping cancer cells survive by recycling their own contents. An old malaria drug blocks that recycling and is being tested in people with no visible cancer but detectable residual cells.
Dozens of companies sell blood tests for tumour DNA and they report different results on the same sample. Government-issued reference samples with known amounts of tumour DNA would expose the differences.
Cancer cells travelling in the blood can be counted. If a drug clears them, that is an early sign it may stop spread, and it reads out in weeks rather than years.
Use an ultra-sensitive blood test after two cycles to decide who needs more than R-CHOP and who can stop early.
37 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 9.3 of 56.