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  • Exploring Morphology and Drug Interactions in Pancreatic Cancer with 3D Cell Culture

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    Shelper_2014_02Thesis.pdf (11.63Mb)
    Author(s)
    Shelper, Todd B.
    Primary Supervisor
    Avery, Vicky
    Other Supervisors
    Stevenson, Graeme
    Year published
    2014
    Metadata
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    Abstract
    Pancreatic cancer continues to have one of the poorest prognoses amongst all cancers, with a 95% mortality rate. Standard of care chemotherapy has failed to provide significant clinical benefits, which has led to the development of targeted agents against validated signalling pathways. However, to date the approach of targeted agents alone, or in combination with traditional chemotherapeutics, has failed to significantly improve the prognosis for pancreatic cancer patients. The current standard of care chemotherapy for advanced pancreatic cancer provides only a modest increase in survival of several months. Models that improve ...
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    Pancreatic cancer continues to have one of the poorest prognoses amongst all cancers, with a 95% mortality rate. Standard of care chemotherapy has failed to provide significant clinical benefits, which has led to the development of targeted agents against validated signalling pathways. However, to date the approach of targeted agents alone, or in combination with traditional chemotherapeutics, has failed to significantly improve the prognosis for pancreatic cancer patients. The current standard of care chemotherapy for advanced pancreatic cancer provides only a modest increase in survival of several months. Models that improve the predictive potential of drug discovery programs and gain greater insights into the complexity of tumour biology are therefore urgently required. To better understand the mechanisms influencing the anti-cancer activities of current and novel therapies, we have developed a 3D in vitro micro-tumour cell culture model. Current in vitro models utilising cell monolayer cultures are unable to recapitulate the biological and physiological complexities of the in vivo pancreatic tumour microenvironment and may be poor predictors of drug efficacy. Pancreatic adenocarcinomas are characterised as having a highly dense and poorly vascularised stroma that is made up of extracellular matrix (ECM) components and host cells. This complex tumour microenvironment has been implicated in the chemoresistance profiles observed in pancreatic tumours.
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    Thesis Type
    Thesis (PhD Doctorate)
    Degree Program
    Doctor of Philosophy (PhD)
    School
    Eskitis Institute for Cell and Molecular Therapies
    DOI
    https://doi.org/10.25904/1912/2223
    Copyright Statement
    The author owns the copyright in this thesis, unless stated otherwise.
    Item Access Status
    Public
    Note
    In order to comply with copyright Figure 1.12 has not been published here.
    Subject
    Pancreatic cancer
    Chemotherapy
    Cell monolayer cultures
    Extracellular matrix (ECM) components and host cells
    Pancreatic tumours
    Publication URI
    http://hdl.handle.net/10072/367976
    Collection
    • Theses - Higher Degree by Research

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