ArticleOncotarget2016
Recurrent AKT mutations in human cancers: functional consequences and effects on drug sensitivity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- Article
- PHENOCAUZ: Linking Human Symptoms, Drug Side Effects and Efficacy to Their Molecular Causes Using Mendelian Disease Biology.bioRxiv : the preprint server for biology · 2026Article
- Review
- The structural heterogeneity of AKT autoinhibition.Protein science : a publication of the Protein Society · 2026Article
- Cell cycle regulation in cancer cells by O-GlcNAcylation.Glycoconjugate journal · 2025Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Kinase signaling cascades: an updated mechanistic landscape.Chemical science · 2025Review
- Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.ACS chemical biology · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Signaling Pathways in Gliomas.Genes · 2025Review
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.Nature biotechnology · 2025Article
- Pro-Apoptotic Effects of Anandamide in Human Gastric Cancer Cells Are Mediated by AKT and ERK Signaling Pathways.International journal of molecular sciences · 2025Article
- Higher risk of recurrence in early-stage breast cancer patients with increased levels of ribosomal protein S6.Scientific reports · 2024Observational
- Review
- Selectivity Studies and Free Energy Calculations of AKT Inhibitors.Molecules (Basel, Switzerland) · 2024Article
- Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination.Genome medicine · 2024Article
- Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations.Orphanet journal of rare diseases · 2023Article
- Review
- The AKT1E17K Allele Promotes Breast Cancer in Mice.Cancers · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Precision oncology trials based on tumor gene sequencing depend on robust knowledge about the phenotypic consequences of the genetic variants identified in patients' tumors. Mutations in AKT1-3 occur in 3-5% of human cancers. Although a single hotspot mutation, E17K, is the most common, well characterized activating mutations account for a minority of Akt variants that have been identified in large tumor sequencing studies to date. In order to determine the potential clinical relevance of both common and rare Akt mutations, we expressed a set of over twenty recurrent Akt mutants in three different cell lines and evaluated activation of Akt pathway signaling and effects on growth. We determined their relative sensitivity to allosteric and ATP-competitive Akt inhibitors in clinical development. Most Akt mutants did not activate pathway signaling compared to wild type Akt and did not affect growth properties. In addition, the most common activating Akt mutations, including Akt1 E17K, L52R, and Q79K conferred neither sensitivity nor resistance to Akt inhibitors. Equivocal evidence was found that Akt1 D323H and Akt2 W80C mutants are relatively resistant to the allosteric Akt inhibitor MK-2206, but not an ATP-competitive inhibitor. Our results suggest that the vast majority of rare Akt variants are passenger mutations with no effect on drug sensitivity. The hypothesis that activating Akt mutations predict for Akt inhibitor sensitivity remains to be tested clinically, but is not yet supported by our preclinical data.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.