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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: Biomarker
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).
Appears in Collections:Scholarly Works - FacM&SPat
Xjenza, 2014, Volume 2, Issue 1
Xjenza, 2014, Volume 2, Issue 1

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