AKT2

Overview

AKT2 is a serine/threonine kinase in the PI3K-AKT-mTOR signaling pathway. It is a paralog of AKT1 and AKT3 and is frequently amplified or overexpressed in diverse cancers. In endometrial carcinoma, AKT2 amplification has been identified as differentially enriched in Black patients relative to White patients, with potential therapeutic implications for pathway-directed therapy.

Alterations observed in the corpus

  • AKT2 amplification was more common in Black endometrial carcinoma (EC) patients than in White patients (9% vs 3%, q<0.01) in a 1,025-patient molecular characterization study at MSK PMID:37651310.
  • AKT2 amplifications associated with shorter overall survival in metastatic PAAD patients receiving first-line chemotherapy (HR_adj = 2.03, P_adj = 0.048) in the MSK PDAC genomic cohort (n=2,336 tumors) PMID:39753968.
  • AKT2 assessed in gallbladder carcinoma (GBC) genomic landscape study PMID:36228155
  • AKT2 somatic mutations detected in breast cancer WES of 100 tumors, part of PI3K/AKT pathway driver landscape PMID:22722201
  • PI3K/AKT pathway mutations (PTEN, AKT1/2, PAX8/PPARG) account for 4.5% (18/402) of papillary thyroid carcinomas in the TCGA PTC cohort PMID:25417114

Cancer types (linked)

  • UCEC — AKT2 amplification enriched in Black patients; contributes to PI3K/AKT/mTOR pathway activation patterns distinct from PTEN/PIK3R1 mutation-driven activation seen in White patients PMID:37651310.
  • PAAD — AKT2 amplification independently associated with shorter OS in metastatic chemotherapy-treated patients PMID:39753968.

Co-occurrence and mutual exclusivity

  • AKT2 amplification co-occurs with other PI3K/AKT pathway alterations and the CN-H/TP53abn molecular subtype that is enriched in Black EC patients PMID:37651310.

Therapeutic relevance

  • AKT2 amplification, alongside lower frequency of PI3K pathway mutations (PTEN, PIK3R1), may reduce eligibility of Black EC patients for some hormonal and PI3K-pathway-targeted therapies while raising the question of AKT inhibitor utility PMID:37651310.

Open questions

  • Whether AKT2 amplification (vs. AKT1 activation) confers differential sensitivity to pan-AKT inhibitors in endometrial carcinoma has not been directly investigated PMID:37651310.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36228155

This page was processed by crosslinker on 2026-05-14. - PMID:22722201

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14.