AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer. This dossier gathers the 3 products (3 approved), 7 trials, 4 pathways and 6 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Serine/threonine kinase; AKT1 E17K is an activating hotspot.
- Breast
- Prostate (PTEN loss)
- Endometrial
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 15-20% | PTEN loss (pathway activation) | Higher in mCRPC (~40%) | cBioPortal (TCGA) |
| HR-positive / HER2-negative breast cancer | 3-5% | AKT1 E17K | ~50% have PIK3CA/AKT1/PTEN alteration combined | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| E17K 17 | Activating | About 3 to 5% of breast cancers | PH-domain mutation that pins AKT1 to the membrane; one of the alterations that qualifies for capivasertib with fulvestrant. | — | Carpten et al., Nature 2007 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: Cancer Hotspots (MSK) · COSMIC: AKT1.
Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Small molecule 3 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| CAPItello-281 NCT04493853 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo | rPFS significantly improved (HR reported at presentation); approved 2026. | |
| COMPETE NCT03049189 | 3 | Positive | Progressive grade 1-2 SSTR-positive GEP-NETs: 177Lu-edotreotide vs everolimus | PFS 23.9 vs 14.1 months, HR 0.67. | |
| evERA NCT05306340 | 3 | Positive | ER+/HER2- advanced breast cancer after CDK4/6 inhibitor: giredestrant + everolimus vs standard endocrine therapy + everolimus | PFS HR 0.56 (ITT); HR 0.38 (ESR1-mutant). | |
| LITESPARK-005 NCT04195750 | 3 | Positive | Advanced clear-cell RCC after PD-1/PD-L1 and VEGF-TKI: belzutifan vs everolimus | PFS HR 0.75; ORR 22.7% vs 3.5%; OS not significant. | |
| CAPItello-291 NCT04305496 | 3 | Positive | HR+/HER2- advanced breast cancer after aromatase inhibitor (± CDK4/6): capivasertib + fulvestrant vs placebo + fulvestrant | PFS HR 0.60 overall; HR 0.50 in AKT-pathway-altered. | |
| CLEAR (KEYNOTE-581) NCT02811861 | 3 | Positive | Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm) | PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79. | |
| RADIANT-3 and RADIANT-4 NCT00510068 | 3 | Positive | Progressive pancreatic NETs (RADIANT-3, n=410) and lung/GI NETs (RADIANT-4, n=302): everolimus vs placebo | PFS HR 0.35 (pNET) and 0.48 (lung/GI). |
Resistance routes that involve this target
Unaddressed routes →PIK3CA mutation, PTEN loss, or AKT1 E17K sustain growth independent of ER.
- Capivasertib, inavolisib, alpelisib, everolimus, gedatolisib by genotype
More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
- AR degraders and N-terminal-domain inhibitors (trials); PSMA radioligand therapy
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
- Taxanes retain activity; N-terminal-domain inhibitors
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
- Platinum-etoposide; DLL3 engagers (tarlatamab) and B7-H3 ADCs in trials
Reciprocal feedback between AR and PI3K pathways.
- Capivasertib + abiraterone (approved 2026 for PTEN-deficient disease)
GR drives an AR-like transcriptional programme under enzalutamide.
- GR antagonists (relacorilant tested in prostate cancer)
Pathways where it is a node
Pathway-to-drug matrix →- Glutamine addictionNode: mTORC1 sensing · 4 druggable nodes
After glucose, glutamine is the tumour's favourite food. It feeds the energy cycle, donates nitrogen for making DNA letters, and makes the antioxidant glutathione. MYC- and KRAS-driven cancers eat so much of it that they starve the T cells next door.
Which nodes have drugs → - Lipid synthesis, uptake & cholesterolNode: SREBP (mTORC1, hypoxia) · 2 druggable nodes
Dividing cells need membranes, and membranes are fat. Cancers switch on the fat-building enzymes most adult tissues keep off, and in fatty environments (breast, omentum, bone marrow) they also steal lipids from neighbouring fat cells. This links obesity to cancer and offers new drug targets.
Which nodes have drugs → - mRNA translation (eIF4F / mTOR)Node: mTORC1 · 1 druggable nodes
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.
Which nodes have drugs → - PI3K / AKT / mTORNode: AKT · 3 druggable nodes
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.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →Query for this target: (TITLE:"AKT" OR ABSTRACT:"AKT" OR TITLE:"AKT1" OR ABSTRACT:"AKT1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about AKT, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/akt.json. Licence CC BY 4.0.