ArticleNature communications2022
Distinct resistance mechanisms arise to allosteric vs. ATP-competitive AKT inhibitors.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Deciphering the Medicinal Chemistry Aspects of Akt Inhibitors for the Management of Cancer: Structure-Activity Relationship Frameworks, Landscapes, and Optimization Approaches.Chemistry & biodiversity · 2026Review
- Network Pharmacology and Molecular Docking ofInternational journal of molecular sciences · 2026Article
- ERG function in prostate cells is regulated by distinct positive feedback loops depending on AKT signaling status.Research square · 2026Article
- Quercetin Inhibits AKT Ser473 Phosphorylation and Disrupts AKT-Androgen Receptor Signaling in Castration-Resistant Prostate Cancer Cells.Antioxidants (Basel, Switzerland) · 2026Article
- PRKG1 hinders myogenic differentiation and predicts response to AKT inhibitor ipatasertib in Rhabdomyosarcoma.Nature communications · 2025Article
- Resistance to Allosteric Inhibitors.Journal of molecular biology · 2025Review
- Scaffold Hopping Method for Design and Development of Potential Allosteric AKT Inhibitors.Molecular biotechnology · 2025Article
- The Precision-Guided Use of PI3K Pathway Inhibitors for the Treatment of Solid Malignancies.Biomedicines · 2025Review
- Pharmacogenomic andFrontiers in pharmacology · 2025Article
- GSTO1 aggravates EGFR-TKIs resistance and tumor metastasis via deglutathionylation of NPM1 in lung adenocarcinoma.Oncogene · 2024Article
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
- Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.Scientific reports · 2024Article
- Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma.Molecular cancer therapeutics · 2024Article
- 2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.Journal of hepatocellular carcinoma · 2024Article
- Ipatasertib exhibits anti‑tumorigenic effects and enhances sensitivity to paclitaxel in endometrial cancerInternational journal of oncology · 2023Article
- Novel Synthetic Derivative of Renieramycin T Right-Half Analog Induces Apoptosis and Inhibits Cancer Stem Cells via Targeting the Akt Signal in Lung Cancer Cells.International journal of molecular sciences · 2023Article
- Upregulation of Receptor Tyrosine Kinase Activity and Stemness as Resistance Mechanisms to Akt Inhibitors in Breast Cancer.Cancers · 2022Article
- Studies on Biological and Molecular Effects of Small-Molecule Kinase Inhibitors on Human Glioblastoma Cells and Organotypic Brain Slices.Life (Basel, Switzerland) · 2022Article
- Genomic mapping of copy number variations influencing immune response in breast cancer.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AKT kinases have emerged as promising therapeutic targets in oncology and both allosteric and ATP-competitive AKT inhibitors have entered clinical investigation. However, long-term efficacy of such inhibitors will likely be challenged by the development of resistance. We have established prostate cancer models of acquired resistance to the allosteric inhibitor MK-2206 or the ATP-competitive inhibitor ipatasertib following prolonged exposure. While alterations in AKT are associated with acquired resistance to MK-2206, ipatasertib resistance is driven by rewired compensatory activity of parallel signaling pathways. Importantly, MK-2206 resistance can be overcome by treatment with ipatasertib, while ipatasertib resistance can be reversed by co-treatment with inhibitors of pathways including PIM signaling. These findings demonstrate that distinct resistance mechanisms arise to the two classes of AKT inhibitors and that combination approaches may reverse resistance to ATP-competitive inhibition.
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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.