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AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
AKT1, AKT2 and AKT3 are serine/threonine kinases at the centre of the PI3K survival pathway, and the AKT1 E17K hotspot is an activating mutation found in about 3 to 5 percent of hormone-receptor-positive breast cancers. Capivasertib (Truqap), a pan-AKT inhibitor, is approved with fulvestrant in HR-positive breast cancer carrying PIK3CA, AKT1 or PTEN alterations (CAPItello-291), a group that makes up around half of such tumours, and from 2026 with abiraterone in PTEN-deficient metastatic prostate cancer (CAPItello-281). PTEN loss activates the pathway in roughly 15 to 20 percent of prostate cancers and around 40 percent of metastatic castration-resistant disease. Hyperglycaemia, diarrhoea and rash are the class toxicities, and whether unselected patients also benefit is contested. In plain terms, AKT is the survival kinase downstream of PI3K, now blocked in breast and prostate cancer.
In plain words · AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
Serine/threonine kinase; AKT1 E17K is an activating hotspot.
4 products aim at AKT: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (AKT1 E17K mutation) absent from normal cells. HPA AKT1: RNA low tissue specificity; high antibody staining in 28 normal tissues; highest cancer staining endometrial cancer (6 of 11 high). HPA AKT2: RNA low tissue specificity; no normal tissue stained high; highest cancer staining breast cancer (9 of 12 high). HPA AKT3: RNA low tissue specificity; high antibody staining in 7 normal tissues; highest cancer staining melanoma (6 of 11 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Prostate cancer); Open Targets associates it with 7 specific cancer types at or above 0.5 (Proteus syndrome, breast cancer, breast adenocarcinoma, breast carcinoma, colorectal adenocarcinoma, ovarian carcinoma and more). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: AKT1 E17K mutation label threshold; Human Protein Atlas AKT1 tissue; Human Protein Atlas AKT2 tissue; Human Protein Atlas AKT3 tissue; Open Targets ENSG00000142208 associations; Open Targets ENSG00000105221 associations
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Serine/threonine kinase; AKT1 E17K is an activating hotspot.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Caudate, Esophagus, Heart muscle, Kidney, Oral mucosa, Parathyroid gland, Prostate.
Medium only: carcinoid, glioma, head and neck cancer, melanoma.
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high.
Medium only: skin cancer, stomach cancer, testis cancer, urothelial cancer.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Breast, Bronchus, Cerebellum, Cervix, Colon, Duodenum, Endometrium.
Medium only: breast cancer, carcinoid, cervical cancer, endometrial cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Triple-negative breast cancer | 20-27% | PI3K-AKT pathway alteration (any of the three) | 28 of 140 first-line metastatic TNBC patients, 20%, in PAKT, where capivasertib gave a progression-free survival hazard ratio of 0.30 in that subgroup (Schmid 2020); cBioPortal: PIK3CA, AKT1 or PTEN mutation or PTEN deep deletion in 47 of 176 samples, 26.7%, in breast_msk_2018. AKT1 mutation alone in 13% of LAR tumours (Bareche 2018), 10 of 299, 3.3%, in brca_metabric and 4 of 176, 2.3%, in breast_msk_2018. LOTUS randomised 124 patients with PTEN-low tumours as a co-primary population (Kim 2017). | doi.org |
| 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.
Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
An intravenous drug that blocks the whole PI3K/mTOR pathway, approved in July 2026 for hormone-positive breast cancer.
Ipatasertib is an experimental small-molecule drug from Hoffmann-La Roche in phase 3 trials for HR-positive / HER2-negative breast cancer and ovarian cancer, aimed at AKT.
The latest in a line of negative targeted-therapy trials in triple-negative disease (EGFR, VEGF, iniparib, now AKT): a modest delay in progression that did not translate into survival, in the same year that an antibody-drug conjugate did. It is why the roadmap treats pathway-targeted small molecules as the road not taken.
It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.
PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
LOTUS and PAKT together made the PI3K/AKT/PTEN-altered subgroup the target population for AKT inhibitors in TNBC; the phase 3 IPATunity130 later failed to confirm it, which is why no AKT inhibitor is approved here.
It made PTEN a protein test rather than a genomic one in this disease, and the concordance between early and late biopsies is the practical point: the diagnostic block usually answers the question, so a fresh biopsy is not needed to make this call.
It is the reason every prostate PI3K or AKT trial gives the drug with abiraterone rather than alone, and the reason PTEN loss is used to select for those combinations rather than as a general prognostic marker.
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.
Shares PI3K, AKT and mTOR inhibitors, Everolimus, PI3K / AKT / mTOR, Neuroendocrine tumours and the tag kinase.
Shares Chronic myeloid leukaemia (KEGG map), Melanoma (KEGG map), Acute myeloid leukaemia (KEGG map), Non-small cell lung cancer (KEGG map) and the tag kinase.
Shares Hallmark: evading growth suppressors, Melanoma (KEGG map), Small cell lung cancer (KEGG map), Non-small cell lung cancer (KEGG map) and the tag kinase.
Shares PI3K / AKT / mTOR and the tag kinase.
Shares Ramon E. Parsons, PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6), Gedatolisib, CAPItello-291 and the tag kinase.
Shares Acute myeloid leukaemia (KEGG map), PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag kinase.
Shares The blood-brain barrier & brain metastasis, Non-small cell lung cancer (KEGG map), PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag kinase.
Shares Acute myeloid leukaemia (KEGG map), Small-molecule kinase inhibitors and the tag kinase.