Identification and modulation of drug targets for precision medicine in breast, lung and ovarian cancer subtypes

Thijs Stutvoet

    Research output: ThesisThesis fully internal (DIV)

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    The introduction of targeted and immunotherapies has improved the treatment of advanced cancers. Targeted therapies directly interact with molecular alterations in cancer cells. Immunotherapy enhances the anti-tumor immune response. Many patients do not yet benefit from these treatment options due to a lack of targetable alterations or the occurrence of resistance to treatment.
    In this thesis, I evaluated whether there are subgroups of patients with breast, lung, or ovarian cancer with targets for targeted therapies or immunotherapy. I described the role of immunotherapy in patients with breast cancer in a literature study. I analyzed gene expression data of lung and ovarian tumors. Using these results, I studied the regulation of the immune checkpoint protein programmed death-ligand 1 (PD-L1) in lung cancer cell lines and tested the usability of a new PET tracer to non-invasively determine PD-L1 expression levels in tumors. In addition, I found signals of biological processes that can be studied as new targets for therapy in high-grade serous ovarian cancer. In cell lines of the clear cell ovarian cancer subtype inhibition of DNA damage signaling was effective. The efficacy was independent of commonly occurring mutations in this ovarian cancer subtype.
    Concluding, gene expression analysis can be used to characterize molecular subtypes of cancers. The efficacy of targeted therapies and immunotherapy may be enhanced by taking novel characteristics of these subtypes into consideration in future studies. The title of the thesis is Identification and modulation of drug targets for precision medicine in breast, lung and ovarian cancer subtypes.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • de Jong, Steven, Supervisor
    • de Vries, Liesbeth, Supervisor
    • Fehrmann, Rudolf, Co-supervisor
    Award date1-Dec-2020
    Place of Publication[Groningen]
    Publication statusPublished - 2020

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