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

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Author(s)
Primary Supervisor
Avery, Vicky
Other Supervisors
Stevenson, Graeme
Year published
2014
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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
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