Translation
Genes are read into RNA, then RNA into protein. mTOR controls the rate, and the short-lived oncoproteins MYC, cyclin D1 and MCL-1 are the first casualties when translation slows.
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.
A factory's single loading dock (eIF4F). No matter how many orders the managers (RAS, PI3K, MYC) shout, everything must pass through the dock. Narrow the dock and the most urgent, oversized orders (oncogene proteins) are the first to fail.
What happens
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.
Genes are read into RNA, then RNA into protein. mTOR controls the rate, and the short-lived oncoproteins MYC, cyclin D1 and MCL-1 are the first casualties when translation slows.
mRNA translation (eIF4F / mTOR). Cancer cells must make protein at furious speed. The eIF4F complex that starts protein synthesis is the funnel where growth signals converge, and drugs that pinch the funnel starve the tumour of the proteins it needs most.
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.
AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
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.
- EverolimusApprovedHR-positive / HER2-negative breast cancerRenal cell carcinomaNeuroendocrine tumours
- CapivasertibApprovedHR-positive / HER2-negative breast cancerProstate cancerMetastatic hormone-sensitive prostate cancer
- GedatolisibApprovedHR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- IpatasertibPhase 3
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- 2021reviewThe plasticity of mRNA translation during cancer progression and therapy resistanceNature Reviews Cancer
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.
- Are eIF4A/eIF4E inhibitors (zotatifin) selectively toxic to tumours in patients?
- Can ribosome biogenesis be targeted with an acceptable window?
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2021reviewThe plasticity of mRNA translation during cancer progression and therapy resistanceNature Reviews Cancer
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 3.7 of 56.