Pancreatic cancer represents less than 3% of cancers diagnosed each year in the United Kingdom yet despite this low number, it is the fifth highest cause of death by cancer. This situation has changed little in the past few decades with median survival barely altering between 1971 and 2007. The availability of well characterised in vivo models that histologically recapitulate pancreatic ductal adenocarcinoma (PDAC) have revolutionised the field of PDAC research. These models not only recapitulate the central epithelial component of human pancreatic cancer but also the incredibly complex microenvironment, a feature for which PDAC is well known. Due to the failure of therapies targeting the neoplastic epithelial cells within PDAC, increasing interest has been given to targeting the tumour microenvironment. The tumour microenvironment is extremely complex and consists of both cellular and non-cellular components and in PDAC exhibits a number of characteristic features including the presence of pancreatic stellate cells. Work in our lab has also highlighted stromal constituents such as lysyl-oxidase and tenascin C which are vital for PDAC viability and/or metastasis. In recent years increasing numbers of stromal targets have been evaluated in mouse models of PDAC with varying success. To date work characterising the stromal changes elicited by targeted therapies has utilised methods which we believe lack the required fastidiousness required to obtain reliable and meaningful results. In this work we have established reliable methods for stromal characterisation, we have established methods to characterise the expression of tenascin C on formalin fixed specimens and we have applied these methods to determine the changes elicited by stromal targeting therapies.
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Characterising the tumour microenvironment in pancreatic cancer and the changes elicited by targeted therapies
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