Pancreatic cancer (PC) is a deadly solid tumor, characterized by late diagnosis, low survival, profound drug resistance, and an oxygen- and nutrient-deprived tumor microenvironment (TME). While the incidence of PC is not particularly high (in Norway approx. 900 patients/year), it is the 4th most common cause of cancer-related death in the Western world, and is predicted to rank 2nd by 2030. Surgery is the only potential cure for PC, however, the majority of PC patients (>80%) are not eligible due to the presence of locally advanced or metastatic disease at diagnosis. For these patients, the only treatment option is chemotherapy.
The conventional chemotherapy (CC) regimens for PC include gemcitabine (GEM) monotherapy and combination therapy of FOLFIRINOX or GEM plus nab-paclitaxel. However, PC rapidly develops resistance to chemotherapy, causing treatment failure and ultimately resulting in limited survival benefit. CC aims at maximally killing treatment-sensitive cancer cells and, consequently, it leaves behind intrinsically resistant cell subpopulations (cells that do not respond to treatment). Due to reduced competition for oxygen and nutrients, these resistant cancer cells proliferate rapidly and as such create a multidrug-resistant disease recurrence. Moreover, the growth of the cancer cells is supported by several factors in the TME, which are not affected by CC and further contribute to the emergence of treatment failure. Thus, to improve treatment outcomes using existing chemotherapeutic agents, this project will investigate the efficacy of a novel, so-called adaptive chemotherapy approach that is based on reduced dose and altered treatment duration combined with therapeutic targeting of tumor-promoting factors from the TME.
The project will be carried out using heterospheroids and monolayer cultures of PC cells and cancer-associated fibroblasts. The following methods will be used: cell culture, fluorescence microscopy, lentiviral transduction, siRNA transfection, assessment of viability and proliferation, drug-sensitivity screening, and expression analysis (immunocytochemistry and western blot).
The project will be carried out at the laboratory facility of the Pancreatic Pathology Research team affiliated with the Department of Pathology, Clinic for Laboratory Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway. The student will work in close collaboration with the main supervisor and other colleagues in the team. For information visit the group’s page: https://www.ous-research.no/gip
Project duration: January 2024 - May 2025