Telomere limits
Chromosome ends shorten with every division, a built-in counter that retires cells after roughly 50 divisions. Cancers reset the counter by switching telomerase back on.
Diagram
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.
The plastic tips on shoelaces fray a little every time you tie them; when they are gone the lace unravels and the shoe is thrown out. Cancer cells carry a machine that keeps re-tipping the laces.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 1, The body's defences: Cancer is not the default.
Chromosome ends shorten with every division, a built-in counter that retires cells after roughly 50 divisions. Cancers reset the counter by switching telomerase back on.
Telomere maintenance & replicative immortality. Normal cells can divide only a limited number of times because the protective caps on their chromosomes, telomeres, wear down. About 90% of cancers switch the cap-rebuilding enzyme telomerase back on, often through TERT promoter mutations, and roughly 10% use an alternative lengthening route (ALT), so they divide indefinitely; imetelstat is the first approved telomerase inhibitor.
The molecular players
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.
ATR is a DNA-damage alarm kinase. Blocking it makes tumours with broken repair systems collapse under their own replication stress.
Where medicines act
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.
- CeralasertibPhase 3
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
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.
- Imetelstat works in MDS; will telomerase inhibition work in solid tumours before the tumour outgrows the patient?
- Can ALT-positive tumours be targeted through their ATR dependence?
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2019reviewTelomeres and telomerase: three decades of progressNature reviews. Genetics
- 2013basicFrequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the diseaseThe Journal of clinical endocrinology and metabolism
- 2006basicBao 2006: glioma stem cells resist radiotherapy by activating the DNA damage responseNature
- 2000reviewThe Hallmarks of Cancer: six capabilities every tumour must acquireCell
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 1.8 of 56.