ArticleScientific reports2019
An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2022Pooled it
- Promoter Hypomethylation Unleashes HMGA1 to Orchestrate Immune Evasion and Therapy Resistance Across Cancers.Biology · 2025Article
- Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.ACS chemical biology · 2025Article
- Computational profiling and virtual screening of MEK inhibitors for triple-negative breast cancer therapy.In silico pharmacology · 2025Article
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer.Journal of advanced research · 2023Review
- Systematic screening identifies ABCG2 as critical factor underlying synergy of kinase inhibitors with transcriptional CDK inhibitors.Breast cancer research : BCR · 2023Article
- Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant.International journal of clinical oncology · 2023Article
- Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.American journal of cancer research · 2021Review
- The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer.International journal of molecular sciences · 2020Review
- Avicularin inhibits cell proliferation and induces cell apoptosis in cutaneous squamous cell carcinoma.Experimental and therapeutic medicine · 2020Article
- Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review.Technology in cancer research & treatmentReview
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor clinical prognosis and limited targeted treatment strategies. Kinase inhibitor screening of a panel of 20 TNBC cell lines uncovered three critical TNBC subgroups: 1) sensitive to only MEK inhibitors; 2) sensitive to only Akt inhibitors; 3) resistant to both MEK/Akt inhibitors. Using genomic, transcriptomic and proteomic datasets of these TNBC cell lines we unravelled molecular features associated with the MEK and Akt drug resistance. MEK inhibitor-resistant TNBC cell lines were discriminated from Akt inhibitor-resistant lines by the presence of PIK3CA/PIK3R1/PTEN mutations, high p-Akt and low p-MEK levels, yet these features could not distinguish double-resistant cells. Gene set enrichment analyses of transcriptomic and proteomic data of the MEK and Akt inhibitor response groups revealed a set of cell cycle-related genes associated with the double-resistant phenotype; these genes were overexpressed in a subset of breast cancer patients. CDK inhibitors targeting the cell cycle programme could overcome the Akt and MEK inhibitor double-resistance. In conclusion, we uncovered molecular features and alternative treatment strategies for TNBC that are double-resistant to Akt and MEK inhibitors.
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Registered trials
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