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Title: | Phospho-Akt expression is high in a subset of triple negative breast cancer patients |
Authors: | Borg, Nigel Baldacchino, Shawn Saliba, Christian Falzon, Sharon DeGaetano, James Scerri, Christian A. Grech, Godfrey |
Keywords: | Biomarkers Breast Cancer -- Malta -- Case studies |
Issue Date: | 2014 |
Publisher: | Malta Chamber of Scientists |
Citation: | Xjenza. 2014, Vol.2(1), p. 51-59 |
Abstract: | The most commonly used biomarkers to predict the response of breast cancer patients to therapy are oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specific therapies such as anti-oestrogen therapy in the event of ER and PgR positivity, and trastuzumab, a monoclonal antibody, in the case of HER2 positive patients. Patients who are negative for all these three biomarkers, the so-called triple negatives, however, derive little benefit from such therapies. The PI3K/Akt pathway is activated in triple negative breast cancer cases, providing a possible target for therapy. The activation of Akt was investigated in Maltese triple negative breast cancer cases using an antibody detecting Akt phosphorylated at serine 473 (anti-Akt pS473). The study showed that 26\% of triple negative breast cancer patients had an elevated level of Akt (pS473). Furthermore, FTY720, a pharmacological activator of the phosphatase PP2A, was shown to block Akt activation at a concentration of 1\textmu M, in HCC1937 cells subjected to insulin-like growth factor 1 (IGF-1). Our data defined a subset of triple negative breast cancer patients based on high activity of AKT (pS473). This subset would be eligible for treatment using therapies which target the PI3K/Akt pathway, such as kinase inhibitors or phosphatase activators. In support of this, the BRCA1 mutant cells (HCC1937) were sensitive to the PP2a activator, FTY720. This suggests that FTY720 is a potential drug for use in adjuvant therapy in breast cancer cases having a high Akt (pS473). |
URI: | https://www.um.edu.mt/library/oar//handle/123456789/2025 |
Appears in Collections: | Scholarly Works - FacM&SPat Xjenza, 2014, Volume 2, Issue 1 Xjenza, 2014, Volume 2, Issue 1 |
Files in This Item:
File | Description | Size | Format | |
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Phospho-Akt expression is high in a subset of Triple Negative Breast Cancer Patients.pdf | 4.74 MB | Adobe PDF | View/Open |
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