Heterogeneity in the pathology of gastrointestinal cancers

Hedde Douwe Biesma

    Research output: PhD ThesisPhD-Thesis - Research and graduation internal

    138 Downloads (Pure)

    Abstract

    Survival remains poor for patients with gastrointestinal cancers. In this PhD thesis we have focused on the ‘Heterogeneity in the pathology of gastrointestinal cancers’. The aim of this thesis was to provide a bespoke stratification by unraveling the intertumor molecular heterogeneity of gastrointestinal cancers. The investigated cancer types were primarily resectable gastric cancers and one chapter tackles chromosomal heterogeneity across metastatic colorectal cancers. All patients with resectable gastric cancer currently receive the same perioperative chemotherapeutic regimen in addition to surgical resection. However, there are large differences in response to chemotherapy and clinical outcome between these patients. In this thesis we have worked under the hypothesis that these differences in outcome could, at least partly, be explained by the intertumor heterogeneity across gastrointestinal cancers. Such intertumor heterogeneity is already taken into account in treatment decisions of metastatic gastrointestinal cancer patients with the availability of markers for targeted therapies, such as human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI-high) or deficient mismatch repair (dMMR), and mutation status of BRAF and RAS genes.1,2 Therefore, detailed molecular characterization aids in a better understanding of the pathology of gastrointestinal cancers and leads to the identification of targets for better prognosis and bespoke treatment modalities. In this thesis, this heterogeneity has been assessed on a histological, molecular, and immunophenotypic level by using a large series of clinical trial tumor specimens of resectable gastric and metastatic colorectal cancer patients.
    Original languageEnglish
    QualificationPhD
    Awarding Institution
    • Vrije Universiteit Amsterdam
    Supervisors/Advisors
    • van Grieken, Nicole Cornelia Theodora, Supervisor, -
    • Ylstra, B., Supervisor, -
    Award date25 Oct 2024
    Print ISBNs9789090389806
    DOIs
    Publication statusPublished - 25 Oct 2024

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