PhD defence A. (Amber) Blaauboer

Dissertation in short::

Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis. Surgery with adjuvant chemotherapy offers the only curative approach for patients with resectable disease.

For many years, gemcitabine was considered as the first-line adjuvant chemotherapeutic agent. However, during the last decade, more effective chemotherapies, such as FOLFIRINOX, have become of interest. A significant disadvantage of these novel systemic therapies are the severe side-effects. Hence, gemcitabine is still being recommended for patients with poor or declining performance status, as it is much better tolerated with less toxicity.

Suboptimal clinical effects are frequently reported in patients treated with gemcitabine and are primarily due to molecular mechanisms limiting the cellular uptake and activation of gemcitabine and thus its overall efficacy.

In this thesis, we aimed to increase gemcitabine efficacy with addition of two different classes of drugs, i.e., interferon-beta (IFN-β) and epi-drugs. Here, we focused on expression of genes involved in gemcitabine transport and metabolism.