Gene

AKT1

AKT serine/threonine kinase 1

Explore in graph →CI-GENE-00000865HGNC:391 ENSG00000142208 NCBI 207 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (19)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–19 of 19 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
AKT1 D323G1
Capivasertib	Malignant Breast Neoplasm	Predictive	C	Supports Sensitivity Response	2	submitted	EID10765 Phase 2 trial of capivasertib in AKT1/2/3 activated solid cancer patients. One pre-treated AKT1 D323G-mutant breast cancer patient with ER-positive HER2-negative mixed ductal and lobular carcinoma had…

Cohorts

Alteration frequency by cohort (110)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved110 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Bladder Cancer (MSK, J Clin Onco 2013) blca_mskcc_solit_2012	Bladder Urothelial Carcinoma	Ssm

Literature

Linked publications (9)

25 per page, newest first.

pubmedPublishedShowing 1–9 of 9 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.
· N Engl J Med · 2023 · PMID 37256976 · validated civic_curation pubmed
AKT Inhibition in Solid Tumors With AKT1 Mutations.
· J Clin Oncol · 2017 · PMID 28489509 · validated civic_curation pubmed
PIK3CA mutation is predictive of poor survival in patients with colorectal cancer.
· Int J Cancer · 2007 · PMID 17590872 · validated civic_curation pubmed
Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy.
· Cancer Discov · 2014 · PMID 24265155 · validated civic_curation pubmed
Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies.

AKT1 E17K6
Akt Inhibitor MK2206	Malignant Breast Neoplasm	Predictive	D	Does Not Support Sensitivity Response	3	accepted	EID231 Breast cancer cell lines with the AKT1 E17K mutation did not show sensitivity to AKT inhibitor MK-2206, unlike cell lines with PIK3CA mutations. PMID 23888070 · Beaver et al., 2013 · Open in CIViC	civic
Capivasertib	Malignant NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID3039 AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363. 58 patients with advanced solid tumors were treated. In patients… (full text at CIViC) PMID 28489509 · Hyman et al., 2017 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	4	submitted	EID9007 In a subprotocol of the NCI-MATCH Trial (EAY131-Y Nonrandomized Trial), 35 patients with AKT E17K Mutant Tumors progressive after Standard therapy received Treatment with capivasertib. Among the patie… (full text at CIViC) PMID 33377972 · Kalinsky et al., 2021 · Open in CIViC	civic
〃	Malignant Breast Neoplasm	Predictive	C	Supports Sensitivity Response	3	accepted	EID709 In a phase-I study of AZD5363, partial response was observed in 2 patients with breast and ovarian carcinoma, respectively, and AKT1 E17K mutations. While full study results have not yet been publishe… (full text at CIViC) PMID 26351323 · Davies et al., 2015 · Open in CIViC	civic
Capivasertib + FulvestrantCombination	HER2 Negative Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	3	submitted	EID12181 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	1	accepted	EID4029 In an in vitro study, a M229 cell line endogenously expressing BRAF V600E mutation (a known vemurafenib sensitizing mutation) and overexpressing AKT1 E17K mutation was associated with resistance to ve… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

AKT1 E17K6

Akt Inhibitor MK2206

Malignant Breast Neoplasm

Predictive

Does Not Support Sensitivity Response

accepted

EID231

Breast cancer cell lines with the AKT1 E17K mutation did not show sensitivity to AKT inhibitor MK-2206, unlike cell lines with PIK3CA mutations.

PMID 23888070 · Beaver et al., 2013 · Open in CIViC

civic

Capivasertib

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

accepted

EID3039

AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363. 58 patients with advanced solid tumors were treated. In patients… (full text at CIViC)

PMID 28489509 · Hyman et al., 2017 · Open in CIViC

civic

〃

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

submitted

EID9007

In a subprotocol of the NCI-MATCH Trial (EAY131-Y Nonrandomized Trial), 35 patients with AKT E17K Mutant Tumors progressive after Standard therapy received Treatment with capivasertib. Among the patie… (full text at CIViC)

PMID 33377972 · Kalinsky et al., 2021 · Open in CIViC

civic

〃

Malignant Breast Neoplasm

Predictive

Supports Sensitivity Response

accepted

EID709

In a phase-I study of AZD5363, partial response was observed in 2 patients with breast and ovarian carcinoma, respectively, and AKT1 E17K mutations. While full study results have not yet been publishe… (full text at CIViC)

PMID 26351323 · Davies et al., 2015 · Open in CIViC

civic

Capivasertib + FulvestrantCombination

HER2 Negative Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

submitted

EID12181

In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC)

PMID 37256976 · Turner et al., 2023 · Open in CIViC

civic

Vemurafenib

Melanoma

Predictive

Supports Resistance

accepted

EID4029

In an in vitro study, a M229 cell line endogenously expressing BRAF V600E mutation (a known vemurafenib sensitizing mutation) and overexpressing AKT1 E17K mutation was associated with resistance to ve… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

AKT1 E17K + BRAF V600EAKT1 BRAF2
Uprosertib	Melanoma	Predictive	D	Supports Sensitivity Response	2	accepted	EID707 A melanoma cell line (M262) with AKT E17K mutation was found to be sensitive to AKT inhibition with GSK2141795B in this study. PMID 24735930 · Lassen et al., 2014 · Open in CIViC	civic
Dabrafenib + UprosertibCombination	Melanoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID13115 A BRAF V600E-positive melanoma cell line (M262) with AKT E17K mutation was found to have a similar level of sensitivity to combination dabrafenib plus AKT inhibitor GSK2141795B (IC50 < 1nM) as to dabr… (full text at CIViC) PMID 24735930 · Lassen et al., 2014 · Open in CIViC	civic

AKT1 E17K + BRAF V600EAKT1 BRAF2

Uprosertib

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID707

A melanoma cell line (M262) with AKT E17K mutation was found to be sensitive to AKT inhibition with GSK2141795B in this study.

PMID 24735930 · Lassen et al., 2014 · Open in CIViC

civic

Dabrafenib + UprosertibCombination

Melanoma

Predictive

Supports Sensitivity Response

submitted

EID13115

A BRAF V600E-positive melanoma cell line (M262) with AKT E17K mutation was found to have a similar level of sensitivity to combination dabrafenib plus AKT inhibitor GSK2141795B (IC50 < 1nM) as to dabr… (full text at CIViC)

PMID 24735930 · Lassen et al., 2014 · Open in CIViC

civic

AKT1 F55Y1
ARQ092 + CapivasertibSubstitutes	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID10766 Expression of AKT1 F55Y in MCF10a and Ba/F3 cells induced p-AKT in Ba/F3 and p-S6, and p-PRAS40 in both cell lines. Treatment with AKT inhibitors capivasertib and ARQ092 decreased cell vaibility and s… (full text at CIViC) PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC	civic

AKT1 F55Y1

ARQ092 + CapivasertibSubstitutes

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

submitted

EID10766

Expression of AKT1 F55Y in MCF10a and Ba/F3 cells induced p-AKT in Ba/F3 and p-S6, and p-PRAS40 in both cell lines. Treatment with AKT inhibitors capivasertib and ARQ092 decreased cell vaibility and s… (full text at CIViC)

PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC

civic

AKT1 L52R1
Capivasertib	Malignant Endometrial NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	4	submitted	EID10762 Phase II trial of AKT-inhibitor capivasertib in patients with solid tumors and AKT1/2/3 alterations. One patient with an AKT1 L52R mutant endometrioid cancer achieved partial response that lasted for … (full text at CIViC) PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC	civic

AKT1 L52R1

Capivasertib

Malignant Endometrial NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID10762

Phase II trial of AKT-inhibitor capivasertib in patients with solid tumors and AKT1/2/3 alterations. One patient with an AKT1 L52R mutant endometrioid cancer achieved partial response that lasted for … (full text at CIViC)

PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC

civic

AKT1 Overexpression1
Vemurafenib	Melanoma	Predictive	D	Does Not Support Resistance	3	accepted	EID6259 An in vitro study of M229 (a human melanoma cell line) endogenously expressing wild-type AKT1 and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells induced to stably over-expre… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

AKT1 Overexpression1

Vemurafenib

Melanoma

Predictive

Does Not Support Resistance

accepted

EID6259

An in vitro study of M229 (a human melanoma cell line) endogenously expressing wild-type AKT1 and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that cells induced to stably over-expre… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

AKT1 P68-C77dup1
Capivasertib	Malignant NeoplasmALIAS	Predictive	D	Supports Sensitivity Response	3	submitted	EID10767 Preclinical study. Expression of AKT1 P68-C77dup in MCF10a cells led to hyper-phosphorylation of AKT1 and growth-factor independent pathway activation. Survival and viability were decreased with AKT … (full text at CIViC) PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC	civic

AKT1 P68-C77dup1

Capivasertib

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

submitted

EID10767

Preclinical study. Expression of AKT1 P68-C77dup in MCF10a cells led to hyper-phosphorylation of AKT1 and growth-factor independent pathway activation. Survival and viability were decreased with AKT … (full text at CIViC)

PMID 35440569 · Shrestha Bhattarai et al., 2022 · Open in CIViC

civic

AKT1 Q79K3
Dabrafenib	Melanoma	Predictive	C	Supports Resistance	4	accepted	EID6260 In a retrospective study of 44 relapsed melanoma patients with BRAF V600E/K (known BRAF inhibitor sensitizing mutations), AKT1 Q79K was associated with acquired resistance to BRAF inhibitor (dabrafeni… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	4	accepted	EID439 The AKT1 Q79K mutation has been shown to confer resistance to BRAF inhibitors (vemurafenib) in melanoma cell line M229. PMID 24265152 · Shi et al., 2014 · Open in CIViC	civic
〃	Melanoma	Predictive	D	Supports Resistance	2	accepted	EID4498 In an in vitro study, a M229 cell line endogenously expressing BRAF V600E mutation (a known vemurafenib sensitizing mutation) and overexpressing AKT1 Q79K mutation was associated with resistance to ve… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

AKT1 Q79K3

Dabrafenib

Melanoma

Predictive

Supports Resistance

accepted

EID6260

In a retrospective study of 44 relapsed melanoma patients with BRAF V600E/K (known BRAF inhibitor sensitizing mutations), AKT1 Q79K was associated with acquired resistance to BRAF inhibitor (dabrafeni… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

Vemurafenib

Melanoma

Predictive

Supports Resistance

accepted

EID439

The AKT1 Q79K mutation has been shown to confer resistance to BRAF inhibitors (vemurafenib) in melanoma cell line M229.

PMID 24265152 · Shi et al., 2014 · Open in CIViC

civic

〃

Melanoma

Predictive

Supports Resistance

accepted

EID4498

In an in vitro study, a M229 cell line endogenously expressing BRAF V600E mutation (a known vemurafenib sensitizing mutation) and overexpressing AKT1 Q79K mutation was associated with resistance to ve… (full text at CIViC)

PMID 24265155 · Shi et al., 2014 · Open in CIViC

civic

AKT1 S473 Phosphorylation1
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Does Not Support Poor Outcome	3	accepted	EID4051 This retrospective study examines outcomes of 158 primary sporadic colorectal cancer patients who had undergone surgical resection and were treated with 5-fluorouracil based chemotherapy. Cytoplasmic … (full text at CIViC) PMID 17590872 · Kato et al., 2007 · Open in CIViC	civic

AKT1 S473 Phosphorylation1

(prognostic)

Malignant Colorectal NeoplasmCURATED_BROADER

Prognostic

Does Not Support Poor Outcome

accepted

EID4051

This retrospective study examines outcomes of 158 primary sporadic colorectal cancer patients who had undergone surgical resection and were treated with 5-fluorouracil based chemotherapy. Cytoplasmic … (full text at CIViC)

PMID 17590872 · Kato et al., 2007 · Open in CIViC

civic

AKT1 Mutation + AKT2 Mutation + MTOR Mutation + PIK3CA Mutation + PTEN MutationMTOR PIK3CA PTEN AKT1 AKT21
Sapanisertib	Solid NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	accepted	EID12075 In this study, 30 patients with advanced solid malignancies harboring mTOR/AKT/PI3K pathway alterations were treated with Sapanisertib. The tumor types included sarcomas, breast, ovarian, head and nec… (full text at CIViC) PMID 38126764 · Subbiah et al., 2024 · Open in CIViC	civic

AKT1 Mutation + AKT2 Mutation + MTOR Mutation + PIK3CA Mutation + PTEN MutationMTOR PIK3CA PTEN AKT1 AKT21

Sapanisertib

Solid NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID12075

In this study, 30 patients with advanced solid malignancies harboring mTOR/AKT/PI3K pathway alterations were treated with Sapanisertib. The tumor types included sarcomas, breast, ovarian, head and nec… (full text at CIViC)

PMID 38126764 · Subbiah et al., 2024 · Open in CIViC

civic

AKT1 Mutation + PIK3CA Mutation + PTEN MutationPIK3CA PTEN AKT11
Capivasertib + FulvestrantCombination	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	3	accepted	EID12020 In a phase 3 trial (NCT04305496) of 708 patients with advanced HR+ HER2- breast cancer, the combination of the AKT inhibitor capivasertib and the estrogen receptor degrader fulvestrant resulted in sig… (full text at CIViC) PMID 37256976 · Turner et al., 2023 · Open in CIViC	civic

AKT1 Mutation + PIK3CA Mutation + PTEN MutationPIK3CA PTEN AKT11

Capivasertib + FulvestrantCombination

Malignant Breast Neoplasm

Predictive

Supports Sensitivity Response

accepted

EID12020

PMID 37256976 · Turner et al., 2023 · Open in CIViC

civic