ArticleBreast cancer research and treatment2019
Combined inhibition of Aurora A and p21-activated kinase 1 as a new treatment strategy in breast cancer.
Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- High Expression of Aurora Kinase A (AURKA) is Associated with Aggressive Tumor Biology and Therapeutic Response in ER+/HER2- Breast Cancer.Annals of surgical oncology · 2026Article
- Cytoskeletal dynamics in breast cancer: mechanistic insights and therapeutic opportunities.Journal of the National Cancer Center · 2026Review
- Aurora kinase as a putative target to tick control.Parasitology · 2024Article
- Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.Frontiers in oncology · 2024Review
- Aurora Kinase A: Integrating Insights into Cancer, Inflammation, and Infectious Diseases.Gut microbes reports · 2024Review
- Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma.Blood science (Baltimore, Md.) · 2023Article
- Emerging roles of Aurora-A kinase in cancer therapy resistance.Acta pharmaceutica Sinica. B · 2023Review
- Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.Biomedicines · 2023Review
- Effects of Ruxolitinib and Calcitriol Combination Treatment on Various Molecular Subtypes of Breast Cancer.International journal of molecular sciences · 2022Article
- Liquid Biopsy as a Diagnostic and Prognostic Tool for Women and Female Dogs with Breast Cancer.Cancers · 2021Article
- Expression of cyclin-dependent kinases and their clinical significance with immune infiltrates could predict prognosis in colorectal cancer.Biotechnology reports (Amsterdam, Netherlands) · 2021Article
- p21-Activated Kinase 1 Promotes Breast TumorigenesisFrontiers in cell and developmental biology · 2021Article
- Single-Cell RNA Sequencing Reveals the Role of Phosphorylation-Related Genes in Hepatocellular Carcinoma Stem Cells.Frontiers in cell and developmental biology · 2021Article
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- Review
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- Review
- Targeting the tyrosine kinase inhibitor-resistant mutant EGFR pathway in lung cancer without targeting EGFR?Translational lung cancer research · 2020Article
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
- The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe serine-threonine kinases Aurora A (AURKA) and p21-activated kinase 1 (PAK1) are frequently overexpressed in breast tumors, with overexpression promoting aggressive breast cancer phenotypes and poor clinical outcomes. Besides the well-defined roles of these proteins in control of cell division, proliferation, and invasion, both kinases support MAPK kinase pathway activation and can contribute to endocrine resistance by phosphorylating estrogen receptor alpha (ERα). PAK1 directly phosphorylates AURKA and its functional partners, suggesting potential value of inhibiting both kinases activity in tumors overexpressing PAK1 and/or AURKA. Here, for the first time, we evaluated the effect of combining the AURKA inhibitor alisertib and the PAK inhibitor FRAX1036 in preclinical models of breast cancer.
methodsCombination of alisertib and FRAX1036 was evaluated in a panel of 13 human breast tumor cell lines and BT474 xenograft model, with assessment of the cell cycle by FACS, and signaling changes by immunohistochemistry and Western blot. Additionally, we performed in silico analysis to identify markers of response to alisertib and FRAX1036.
resultsPharmacological inhibition of AURKA and PAK1 synergistically decreased survival of multiple tumor cell lines, showing particular effectiveness in luminal and HER2-enriched models, and inhibited growth and ERα-driven signaling in a BT474 xenograft model. In silico analysis suggested cell lines with dependence on AURKA are most likely to be sensitive to PAK1 inhibition.
conclusionDual targeting of AURKA and PAK1 may be a promising therapeutic strategy for treatment of breast cancer, with a particular effectiveness in luminal and HER2-enriched tumor subtypes.
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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.