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AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer. This dossier gathers the 4 products (3 approved), 43 trials, 10 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.
Serine/threonine kinase; AKT1 E17K is an activating hotspot.
| 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.
| 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.
| Modality | Approved | Phase 3 |
|---|---|---|
| Small molecule 4 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib/+Paclitaxel vs Placebo+Paclitaxel as First-line Treatment for Patients With Locally Advanced (Inoperable) or Metastatic TNBC. | Overall survival 17.7 vs 18.0 months (HR 0.92, p 0.32) overall and 20.4 vs 20.4 months (HR 1.05) in PIK3CA/AKT1/PTEN-altered tumours; PFS 5.6 vs 5.1 months (HR 0.72). | ||
CAPItello-281 NCT04493853 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo | Median rPFS 33.2 against 25.7 months, HR 0.81 (95% CI 0.66 to 0.98, p=0.034); OS HR 0.90 at 26.4% maturity; 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). | |
IPATunity130 NCT03337724 | 3 | Negative | PIK3CA, AKT1 or PTEN-altered locally advanced unresectable or metastatic triple-negative breast cancer, no prior chemotherapy for advanced disease: first-line paclitaxel with ipatasertib or placebo (cohort A), 30 countries including the United Kingdom | PFS 7.4 vs 6.1 months (HR 1.02, 0.71 to 1.45); OS 24.4 vs 24.9 months (HR 1.08). Negative. | |
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. | |
CheckMate 025 NCT01668784 | 3 | Positive | Advanced clear cell renal cell carcinoma after one or two anti-angiogenic therapies: nivolumab against everolimus | Nivolumab improved overall survival and response rate over everolimus in previously treated clear cell renal cell carcinoma; approved in November 2015. | |
BOLERO-2 NCT00863655 | 3 | Positive | Postmenopausal hormone receptor-positive, HER2-negative advanced breast cancer after a non-steroidal aromatase inhibitor: exemestane with everolimus or placebo | Everolimus plus exemestane more than doubled progression-free survival compared with exemestane alone; approved in July 2012. | |
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). | |
| 3 | Active | A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With HR+ / HER2- Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain | - | ||
| 3 | Recruiting | An Open-Label, Multicenter Extension Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Study | - | ||
| 3 | Active | A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292) | - | ||
| 3 | Active | A Phase IIIb Single Arm, 2 Cohorts Study Assessing the Efficacy and Safety of Capivasertib+ Fulvestrant as Treatment for Locally Advanced(Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With Endocrine Therapy in Chinese Patients | - | ||
| 3 | Recruiting | Efficacy, Safety and Patient-reported Outcomes of Peptide Receptor Radionuclide Therapy With 177Lu-edotreotide Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus. | - | ||
| 3 | Active | Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy | - | ||
| 3 | Active | A Prospective, Randomised, Controlled, Open-label, Multicentre Study to Evaluate Efficacy, Safety and Patient-Reported Outcomes of Peptide Receptor Radionuclide Therapy (PRRT) With 177Lu-Edotreotide Compared to Best Standard of Care in Patients With Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor-Positive (SSTR+), Neuroendocrine Tumours of GastroEnteric or Pancreatic Origin | - | ||
| 3 | Recruiting | VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Gedatolisib With Endocrine Therapy and Palbociclib vs Endocrine Therapy and Ribociclib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer | - | ||
| 3 | Active | A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) | - | ||
| 2/3 | Recruiting | Phase II/III Study to Evaluate the Safety and Efficacy of Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) | - | ||
NCI-MATCH (EAY131) NCT02465060 | platform | Active | Advanced solid tumours, lymphomas and myeloma that have progressed on standard treatment: central tumour sequencing assigns patients to one of nearly 40 single-agent or doublet targeted-therapy arms by molecular alteration regardless of cancer type | 5,954 patients enrolled; 17.8 percent assigned to an arm. Dabrafenib plus trametinib in BRAF V600 tumours (38 percent response) and nivolumab in dMMR non-colorectal tumours (36 percent) were positive; most single-agent arms were not. | |
CUPISCO NCT03498521 | 2 | Positive | Newly diagnosed unfavourable cancer of unknown primary controlled by three cycles of platinum chemotherapy: randomised to molecularly guided therapy chosen from tissue and blood genomic profiling, or to continued chemotherapy | Median progression-free survival 6.1 months with molecularly guided therapy versus 4.4 months with continued chemotherapy (hazard ratio 0.72); overall survival immature. | |
National Lung Matrix Trial NCT02664935 | 2 | Completed | Advanced non-small-cell lung cancer after first-line treatment, screened nationally through the Cancer Research UK Stratified Medicine Programme: 22 biomarker-defined cohorts of eight targeted drugs | Most of the 22 biomarker-drug cohorts did not meet their pre-set efficacy thresholds; the trial demonstrated national molecular screening and the limits of single-agent matching. | |
PAKT NCT02423603 | 2 | Positive | Untreated metastatic triple-negative breast cancer: first-line paclitaxel with capivasertib or placebo, UK-led academic phase 2 at 30 UK hospitals and sites in France, Georgia, Hungary, Romania and South Korea | PFS 5.9 vs 4.2 months (HR 0.74); OS 19.1 vs 12.6 months (HR 0.61, p 0.04); PIK3CA/AKT1/PTEN-altered PFS 9.3 vs 3.7 months (HR 0.30). Not confirmed by CAPItello-290. | |
plasmaMATCH NCT03182634 | 2 | Completed | Advanced breast cancer across the United Kingdom: circulating tumour DNA testing of a blood sample assigns patients with ESR1, HER2 or AKT1 mutations or PTEN loss to matched treatment cohorts, with a later cohort for triple-negative disease | Circulating tumour DNA matched tissue genotyping with about 93 percent sensitivity; neratinib (HER2 mutations) and capivasertib plus fulvestrant (AKT1 mutations, receptor-positive) met their response thresholds; extended-dose fulvestrant for ESR1 mutations did not. | |
LOTUS NCT02162719 | 2 | Positive | Untreated inoperable locally advanced or metastatic triple-negative breast cancer: first-line paclitaxel with ipatasertib or placebo, 44 hospitals in eight countries | PFS 6.2 vs 4.9 months (HR 0.60, p 0.037); PTEN-low 6.2 vs 3.7 months (HR 0.59, p 0.18). Not confirmed by IPATunity130. | |
| 2 | Active | A Phase II, Open-Label, Multicenter, Platform Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors | - | ||
BARBICAN NCT05498896 | 2 | Active | Triple-negative breast cancer: randomised open-label phase 2 of neoadjuvant paclitaxel then doxorubicin and cyclophosphamide with atezolizumab, with or without the AKT inhibitor ipatasertib, Barts Health London | - | |
| 2 | Planned | The Combination of Everolimus and PD-1 in the Treatment of Locally Advanced and Advanced Colorectal Cancer That Cannot be R0 Resected | - |
PIK3CA mutation, PTEN loss, or AKT1 E17K sustain growth independent of ER.
More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
Reciprocal feedback between AR and PI3K pathways.
GR drives an AR-like transcriptional programme under enzalutamide.
KEGG's AML map shows the two hits that turn a normal blood stem cell into a leukaemia: a growth signal jammed on (FLT3, KIT or RAS) plus a broken maturation switch (fusion proteins such as PML-RARA or AML1-ETO, or mutated CEBPA and RUNX1). Drugs now exist for both halves.
Which nodes have drugs →KEGG's CML map is built around one fusion protein, BCR-ABL1, a kinase that never switches off and drives RAS, PI3K and STAT5 signalling. Because a single enzyme causes the disease, a single class of pill (imatinib and its successors) controls it in most patients.
Which nodes have drugs →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 →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 →KEGG's melanoma map shows BRAF or NRAS mutations driving the MAPK growth relay, PTEN loss driving PI3K/AKT, and loss of the CDKN2A brakes (p16 and p14ARF) on CDK4/6 and p53. BRAF plus MEK inhibitors and immune checkpoint antibodies have transformed treatment.
Which nodes have drugs →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 →KEGG's non-small cell lung cancer map shows a set of alternative on-switches (EGFR mutation, KRAS mutation, EML4-ALK, RET and MET alterations) that all feed the same RAS/ERK, PI3K/AKT and STAT relays, plus loss of the p16 and p53 brakes. Each on-switch now has its own targeted pill, which is why molecular testing comes before treatment.
Which nodes have drugs →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 →KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.
Which nodes have drugs →KEGG's small cell lung cancer map shows a tumour with both master brakes removed, RB1 and TP53, plus amplified MYC pushing the cell cycle and PTEN loss and BCL2 keeping cells alive. Chemotherapy with PD-L1 antibodies and the DLL3 T-cell engager tarlatamab are the current answers.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/akt.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-NC 4.0.