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  • The CCL5-CCR5 Axis in Breast Cancer

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    Sax_2015_02Thesis.pdf (5.842Mb)
    Author(s)
    Sax, Michael
    Primary Supervisor
    Mellick, Albert
    Wei, Ming
    Year published
    2015
    Metadata
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    Abstract
    Cancer is one of the leading underlying causes of death worldwide. Despite decades of research, cancer is predicted to be the leading cause of death by the year 2020. Anti angiogenic therapies that target the key signalling molecule, vascular endothelial growth factor (VEGF) have shown promise in the treatment of some solid tumours, resulting in increased progression-free survival times in patients. However, there are several significant problems with current anti-angiogenic therapies, such as the phenomenon of resistance. Tumours can be divided into those that are intrinsically nonresponsive to therapy, and those that do ...
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    Cancer is one of the leading underlying causes of death worldwide. Despite decades of research, cancer is predicted to be the leading cause of death by the year 2020. Anti angiogenic therapies that target the key signalling molecule, vascular endothelial growth factor (VEGF) have shown promise in the treatment of some solid tumours, resulting in increased progression-free survival times in patients. However, there are several significant problems with current anti-angiogenic therapies, such as the phenomenon of resistance. Tumours can be divided into those that are intrinsically nonresponsive to therapy, and those that do respond. However, for those tumours that do respond to therapy, an initial positive response (tumour regression) is followed by tumour re-vascularisation and rapid relapse. Secondly, anti-angiogenic therapies target normal physiological processes, including vascular homeostasis, wound healing and the immune system, leading to a range of potentially negative side effects, including death. Thus unravelling the biology of angiogenesis and developing new drug targets is a priority of current research. The C-C chemokine receptor 5 (CCR5) has been the subject of extensive research in the last few years. This is primarily because of its association with the pathology of disease, viral infection, and the immune response. However, while the main ligand for CCR5, C C chemokine ligand 5 (CCL5) is known to be upregulated in malignant breast cancer, little has been done to unravel the CCL5-CCR5 axis in breast cancer and its potential role as a driver of malignancy. Furthermore, while experimental evidence, including data from CCR5 knockout mouse, suggests a role for CCL5-CCR5 in neovascularisation, little has been done to study the potential role of CCL5-CCR5 in tumour angiogenesis, as well as implications CCL5-CCR5 signalling may have on clinical course in breast cancer.
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    Thesis Type
    Thesis (PhD Doctorate)
    Degree Program
    Doctor of Philosophy (PhD)
    School
    School of Medical Science
    DOI
    https://doi.org/10.25904/1912/3697
    Copyright Statement
    The author owns the copyright in this thesis, unless stated otherwise.
    Item Access Status
    Public
    Subject
    C-C chemokine receptor 5 (CCR5)
    Breast cancer
    Anti angiogenic therapies
    Vascular endothelial growth factor (VEGF)
    Publication URI
    http://hdl.handle.net/10072/365646
    Collection
    • Theses - Higher Degree by Research

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