Optimal targeting of HER2-PI3K signaling in breast cancer: Mechanistic insights and clinical implications
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Summary
The combination of a PI3K inhibitor with trastuzumab has been shown to be effective at overcoming trastizumab resistance in models of HER2(+) breast cancer by inhibiting HER2-PI3K-FOXO-survivin signaling.
- Type
- article
- Published
- 2013-06-21
- Cited by
- 54
- References
- 35
- Access
- Open access
- OpenAlex
- https://openalex.org/W23794708
- Semantic Scholar
- https://api.semanticscholar.org/CorpusID:11445176
Keywords
Mathematics, Algorithm, Graph, Base (topology), Computer science
References
- The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.
- PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer.
- Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action.
- Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.
- HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion
- Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer.
- Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer
- Helical domain and kinase domain mutations in p110α of phosphatidylinositol 3-kinase induce gain of function by different mechanisms
- Targeting breast cancer stem cells.
- Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors
- Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications
- A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.
- Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
- NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations.
- Human Breast Cancer Cells Selected for Resistance to Trastuzumab In vivo Overexpress Epidermal Growth Factor Receptor and ErbB Ligands and Remain Dependent on the ErbB Receptor Network
- Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer
- Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors
- Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
- Tumor-Initiating Cells of HER2-Positive Carcinoma Cell Lines Express the Highest Oncoprotein Levels and Are Sensitive to Trastuzumab
- Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy.
Cited by
- Breast cancer stem cells: current advances and clinical implications.
- The PI3K Pathway as a Therapeutic Target in Breast Cancer
- hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells
- Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy
- Clinical Implications of Mutations in the PI3K Pathway in HER2+ Breast Cancer: Prognostic or Predictive?
- Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression
- The CBM Complex Underwrites NF-κB Activation to Promote HER2-Associated Tumor Malignancy
- Cancer stem cell-driven efficacy of trastuzumab (Herceptin): towards a reclassification of clinically HER2-positive breast carcinomas
- Targeted pathways in breast cancer: molecular and protein markers guiding therapeutic decisions.
- ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics
- Afucosylated Antibodies Increase Activation of FcγRIIIa-Dependent Signaling Components to Intensify Processes Promoting ADCC
- PI3K and Cancer: Lessons, Challenges and Opportunities
- The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulin β1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway.
- Amyloid-β precursor protein promotes cell proliferation and motility of advanced breast cancer
- Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms.
- Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in the NSABP B-31 trial.
- HER2 in solid tumors: more than 10 years under the microscope; where are we now?
- Where cancer genomics should go next: a clinician's perspective.
- Serum and Glucocorticoid-Regulated Kinase Signaling in Breast Cancer
- Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention
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