{"entity":{"id":"akt","kind":"target","name":"AKT","aka":[],"tldr":"AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Protein_kinase_B","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Protein_kinase_B"}],"tags":["kinase"],"related":["akt1-e17k"],"cancers":["breast-hr-positive","prostate","tnbc"],"sections":[],"technologies":["pi3k-akt-mtor-inhibitors"],"targets":[],"drugs":["ipatasertib"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","aml-signalling","cml-signalling","melanoma-signalling","nsclc-signalling","prostate-cancer-signalling","sclc-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-schmid-pakt-capivasertib-tnbc-jco-2020","paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: PIK3CA, AKT1 or PTEN altered in 20% of PAKT patients, in whom capivasertib gave a progression-free survival hazard ratio of 0.30 (Schmid 2020), and in 26.7% of 176 MSK triple-negative samples (cBioPortal); the phase 3 trials IPATunity130 and CAPItello-290 did not confirm the phase 2 signals, so no AKT inhibitor is approved in TNBC."],"symbol":"AKT1/2/3","role":[],"sources":[],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"AKT1 E17K mutation label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"AKT1 alteration (with PIK3CA and PTEN as the qualifying set)"},{"label":"Human Protein Atlas AKT1 tissue","url":"https://www.proteinatlas.org/ENSG00000142208-AKT1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas AKT2 tissue","url":"https://www.proteinatlas.org/ENSG00000105221-AKT2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas AKT3 tissue","url":"https://www.proteinatlas.org/ENSG00000117020-AKT3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000142208 associations","url":"https://platform.opentargets.org/target/ENSG00000142208/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000105221 associations","url":"https://platform.opentargets.org/target/ENSG00000105221/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"Serine/threonine kinase; AKT1 E17K is an activating hotspot.","whereFound":["Breast","Prostate (PTEN loss)","Endometrial","Triple-negative breast cancer: pi3k-akt pathway alteration (any of the three) 20-27%"],"targetClass":"kinase","prevalence":[{"cancerId":"breast-hr-positive","pct":"3-5","measure":"AKT1 E17K","source":"https://www.cbioportal.org/study/summary?id=brca_tcga_pan_can_atlas_2018","note":"~50% have PIK3CA/AKT1/PTEN alteration combined"},{"cancerId":"prostate","pct":"15-20","measure":"PTEN loss (pathway activation)","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"Higher in mCRPC (~40%)"},{"cancerId":"tnbc","pct":"20-27","measure":"PI3K-AKT pathway alteration (any of the three)","source":"https://doi.org/10.1200/JCO.19.00368","note":"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)."}]},"route":"/targets/akt/","neighbours":{"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"},{"id":"gedatolisib","kind":"drug","name":"Gedatolisib","route":"/drugs/gedatolisib/"},{"id":"ipatasertib","kind":"drug","name":"Ipatasertib","route":"/drugs/ipatasertib/"}],"pathway":[{"id":"aml-signalling","kind":"pathway","name":"Acute myeloid leukaemia (KEGG map)","route":"/pathways/aml-signalling/"},{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"cml-signalling","kind":"pathway","name":"Chronic myeloid leukaemia (KEGG map)","route":"/pathways/cml-signalling/"},{"id":"glutamine-metabolism","kind":"pathway","name":"Glutamine addiction","route":"/pathways/glutamine-metabolism/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"},{"id":"melanoma-signalling","kind":"pathway","name":"Melanoma (KEGG map)","route":"/pathways/melanoma-signalling/"},{"id":"mrna-translation-eif4f","kind":"pathway","name":"mRNA translation (eIF4F / mTOR)","route":"/pathways/mrna-translation-eif4f/"},{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"},{"id":"blood-brain-barrier-metastasis","kind":"pathway","name":"The blood-brain barrier & brain metastasis","route":"/pathways/blood-brain-barrier-metastasis/"}],"paper":[{"id":"paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","kind":"paper","name":"Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial","route":"/key-papers/paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026/"},{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","route":"/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/"},{"id":"paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","kind":"paper","name":"Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","route":"/key-papers/paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017/"},{"id":"paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","kind":"paper","name":"IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/"},{"id":"paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","kind":"paper","name":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","route":"/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/"},{"id":"paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011","kind":"paper","name":"Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","route":"/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/"},{"id":"paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","kind":"paper","name":"Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis","route":"/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/"}],"trial":[{"id":"barbican","kind":"trial","name":"BARBICAN","route":"/trials/barbican/"},{"id":"capitello-281","kind":"trial","name":"CAPItello-281","route":"/trials/capitello-281/"},{"id":"capitello-291","kind":"trial","name":"CAPItello-291","route":"/trials/capitello-291/"},{"id":"ipatunity130","kind":"trial","name":"IPATunity130","route":"/trials/ipatunity130/"},{"id":"lotus","kind":"trial","name":"LOTUS","route":"/trials/lotus/"},{"id":"pakt","kind":"trial","name":"PAKT","route":"/trials/pakt/"}],"pairing":[{"id":"pi3k-pathway-plus-endocrine","kind":"pairing","name":"PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)","route":"/pairings/pi3k-pathway-plus-endocrine/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"person":[{"id":"nicholas-turner","kind":"person","name":"Nicholas Turner","route":"/people/nicholas-turner/"},{"id":"ramon-parsons","kind":"person","name":"Ramon E. Parsons","route":"/people/ramon-parsons/"}],"term":[{"id":"evading-growth-suppressors","kind":"term","name":"Hallmark: evading growth suppressors","route":"/terms/evading-growth-suppressors/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"}]}}