ArticleScience signaling2014
Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K-Akt pathway in triple-negative breast cancer.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 164 citations in OpenAlex.
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- PLSCR1 drives chemoresistance in TNBC via METTL3/IGF2BP3-mediated mRNA stabilization and EGFR-MAPK pathway activation.Cell death & disease · 2026Article
- Deep interpretable radiogenomic workflow deciphers tumor microenvironment from breast MRI and identifies clinician-interpretable biomarkers.NPJ precision oncology · 2026Article
- Evolving antibody-drug conjugates in breast cancer from precision delivery to tumor microenvironment reprogramming.Journal of hematology & oncology · 2026Review
- OTUD4 deubiquitination stabilizes EGFR and activates the PI3K/AKT pathway to promote the invasiveness of triple-negative breast cancer.Cell death & disease · 2026Article
- Recent advances in bispecific antibody-drug conjugates for breast cancer therapy.Cancer chemotherapy and pharmacology · 2026Review
- Article
- Pinocembrin as a novel anti-cancer agent: Exploring preclinical evidence along with therapeutic potential.World journal of experimental medicine · 2025Review
- Patritumab deruxtecan in breast cancer treatment: a drug evaluation.Future oncology (London, England) · 2025Review
- HER3 promotes triple-negative breast cancer progression by upregulating PHF8 via miR-34b-5p-dependent mechanism.Cell death & disease · 2025Article
- EGFR amplification and PI3K pathway mutations identify a subset of breast cancers that synergistically respond to EGFR and PI3K inhibition.bioRxiv : the preprint server for biology · 2025Article
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- PCSK9 Promotes the Malignancy of Triple-negative Breast Cancer Cells by Reducing Cholesterol Levels at the Plasma Membrane to Activate EGFR and HER3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Article
- A first-in-class selective inhibitor of EGFR and PI3K offers a single-molecule approach to targeting adaptive resistance.Nature cancer · 2024Article
- HER3 receptor and its role in the therapeutic management of metastatic breast cancer.Journal of translational medicine · 2024Review
- Breast Cancer Treatment Strategies Targeting the Tumor Microenvironment: How to Convert "Cold" Tumors to "Hot" Tumors.International journal of molecular sciences · 2024Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Patient-specific signaling signatures predict optimal therapeutic combinations for triple negative breast cancer.Molecular cancer · 2024Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
Abstract
Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common and therapeutically targeted in triple-negative breast cancer (TNBC). However, activation of another EGFR family member [human epidermal growth factor receptor 3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs. We found that TNBC cell lines cultured with the EGFR or HER3 ligand EGF or heregulin, respectively, and treated with either an Akt inhibitor (GDC-0068) or a PI3K inhibitor (GDC-0941) had increased abundance and phosphorylation of HER3. The phosphorylation of HER3 and EGFR in response to these treatments was reduced by the addition of a dual EGFR and HER3 inhibitor (MEHD7945A). MEHD7945A also decreased the phosphorylation (and activation) of EGFR and HER3 and the phosphorylation of downstream targets that occurred in response to the combination of EGFR ligands and PI3K-Akt pathway inhibitors. In culture, inhibition of the PI3K-Akt pathway combined with either MEHD7945A or knockdown of HER3 decreased cell proliferation compared with inhibition of the PI3K-Akt pathway alone. Combining either GDC-0068 or GDC-0941 with MEHD7945A inhibited the growth of xenografts derived from TNBC cell lines or from TNBC patient tumors, and this combination treatment was also more effective than combining either GDC-0068 or GDC-0941 with cetuximab, an EGFR-targeted antibody. After therapy with EGFR-targeted antibodies, some patients had residual tumors with increased HER3 abundance and EGFR/HER3 dimerization (an activating interaction). Thus, we propose that concomitant blockade of EGFR, HER3, and the PI3K-Akt pathway in TNBC should be investigated in the clinical setting.
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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.