PI3K/AKT/mTOR
The 'grow and survive' circuit: PI3K to AKT to mTOR, with PTEN as the off switch. The most frequently altered pathway in cancer, and one of the hardest to drug without hitting blood sugar and skin.
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.
Think of a factory: the receptor is the order desk, PI3K and AKT are the managers relaying the order, PTEN is the accountant cancelling orders, and mTOR is the assembly line. Cancer forges orders (PIK3CA mutation) or fires the accountant (PTEN loss).
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.
The 'grow and survive' circuit: PI3K to AKT to mTOR, with PTEN as the off switch. The most frequently altered pathway in cancer, and one of the hardest to drug without hitting blood sugar and skin.
PI3K / AKT / mTOR. The cell's 'grow and survive' circuit. Growth signals from the surface switch on PI3K, which switches on AKT, which switches on mTOR, which builds proteins and blocks self-destruction.
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.
PIK3CA is the most commonly mutated gene in hormone-driven breast cancer. Drugs against it work, but hitting it cleanly without raising blood sugar took years.
AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
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.
- AlpelisibApprovedHR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- CapivasertibApprovedHR-positive / HER2-negative breast cancerProstate cancerMetastatic hormone-sensitive prostate cancer
- EverolimusApprovedHR-positive / HER2-negative breast cancerRenal cell carcinomaNeuroendocrine tumours
- GedatolisibApprovedHR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- InavolisibApprovedHR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- DuvelisibApprovedChronic lymphocytic leukaemiaPeripheral T-cell lymphomas (including cutaneous T-cell lymphoma)
- IdelalisibApprovedChronic lymphocytic leukaemiaFollicular lymphomaRelapsed or refractory chronic lymphocytic leukaemia
- therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)ApprovedColorectal cancerNon-small-cell lung cancerHR-positive / HER2-negative breast cancer
- +5 more at PIK3CA / PI3K-alpha →
- IpatasertibPhase 3
- AfatinibApprovedNon-small-cell lung cancerEGFR-mutated non-small-cell lung cancerHER2-mutant non-small-cell lung cancer
- Disitamab vedotinApprovedGastric & gastro-oesophageal junction cancerBladder & urothelial cancer
- HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)ApprovedHER2-positive breast cancerHR-positive / HER2-negative breast cancerGastric & gastro-oesophageal junction cancer
- InetetamabApprovedHER2-positive breast cancer
- LapatinibApprovedHER2-positive breast cancerHER2-positive breast cancer with brain metastases
- MargetuximabApprovedHER2-positive breast cancer
- NeratinibApprovedHER2-positive breast cancerHER2-positive breast cancer with brain metastases
- PertuzumabApprovedHER2-positive breast cancerEarly HER2-positive breast cancer
- +35 more at HER2 →
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.
- Can mutant-selective PI3Kα inhibitors avoid hyperglycaemia and widen the window?
- Why do PTEN-loss tumours respond less than PIK3CA-mutant ones?
Key evidence
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 3.5 of 56.