ArticleCancers2021
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Therapeutic targeting of RAGE/STAT3 signaling abrogates S100A7-driven breast tumorigenicity and immune suppression.Breast cancer research : BCR · 2026Article
- Eugenoplatin (a phyto-chemo drug conjugate) targets cancer stem cells through inhibition of the β-catenin signaling in triple-negative breast cancer cells.Journal of translational medicine · 2026Article
- Tailored therapies for triple-negative breast cancer: current landscape and future perceptions.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- JAK2 Inhibition Augments the Anti-Proliferation Effects by AKT and MEK Inhibition in Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer.Scientific reports · 2025Article
- Identifying drug candidates for pancreatic ductal adenocarcinoma based on integrative multiomics analysis.Journal of gastrointestinal oncology · 2024Article
- Endogenous pAKT activity is associated with response to AKT inhibition alone and in combination with immune checkpoint inhibition in murine models of TNBC.Cancer letters · 2024Article
- Boolean modeling of breast cancer signaling pathways uncovers mechanisms of drug synergy.PloS one · 2024Article
- Integrated Transcriptome and Molecular Docking to Identify the Hub Superimposed Attenuation Targets of Curcumin in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- MicroRNA-Based Discovery of Biomarkers, Therapeutic Targets, and Repositioning Drugs for Breast Cancer.Cells · 2023Article
- New Biomarkers and Treatment Advances in Triple-Negative Breast Cancer.Diagnostics (Basel, Switzerland) · 2023Review
- Therapeutic Implications of the Drug Resistance Conferred by Extracellular Vesicles Derived from Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2023Review
- Upregulation of the ferroptosis-relatedFrontiers in oncology · 2023Article
- Article
- AT7867 Inhibits the Growth of Colorectal Cancer Stem-Like Cells and Stemness by Regulating the Stem Cell Maintenance Factor Ascl2 and Akt Signaling.Stem cells international · 2023Article
- Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer.Frontiers in cell and developmental biology · 2023Article
- Overview on Current Trends and Emerging Therapies in the Chemotherapy of Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.Galen medical journal · 2023Review
- BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.Frontiers in oncology · 2023Review
- ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells.Cancers · 2022Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
There is an unmet medical need for the development of new targeted therapeutic strategies for triple-negative breast cancer (TNBC). With drug combination screenings, we found that the triple combination of the protein kinase inhibitors (PKIs) of the epidermal growth factor receptor (EGFR), v-akt murine thymoma viral oncogene homolog (AKT), and MAPK/ERK kinase (MEK) is effective in inducing apoptosis in TNBC cells. A set of PKIs were first screened in combination with gefitinib in the TNBC cell line, MDA-MB-231. The AKT inhibitor, AT7867, was identified and further analyzed in two mesenchymal stem-like (MSL) subtype TNBC cells, MDA-MB-231 and HS578T. A combination of gefitinib and AT7867 reduced the proliferation and long-term survival of MSL TNBC cells. However, gefitinib and AT7867 induced the activation of the rat sarcoma (RAS)/ v-raf-1 murine leukemia viral oncogene homolog (RAF)/MEK/ extracellular signal-regulated kinase (ERK) pathway. To inhibit this pathway, MEK/ERK inhibitors were further screened in MDA-MB-231 cells in the presence of gefitinib and AT7867. As a result, we identified that the MEK inhibitor, PD-0325901, further enhanced the anti-proliferative and anti-clonogenic effects of gefitinib and AT7867 by inducing apoptosis. Our results suggest that the dual inhibition of the AKT and MEK pathways is a novel potential therapeutic strategy for targeting EGFR in TNBC cells.
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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.