Abstract

Background: Pancreatic cancer is a devastating disease and new, personalized approaches for treatment are much-needed. Organoids are a new promising advance on this road. We have used pancreatic cancer organoids for pharmacotyping. The aim of this pilot was to find individually best suitable drugs amongst clinically relevant alternatives. The long term aim is to improve prognosis and decrease the use of drugs that are ineffective on individual patients. Material & Methods: Five pancreatic tumour patients operated at Helsinki University Hospital were enrolled in the study. Samples of cancer and normal tissue were taken during the operation. Samples were minced and digested into single cells and cultured into organoids in Matrigel. Pharmacotyping was done with gemcitabine, paclitaxel, FOLFIRINOX and trametinib. DMSO was used as control. We measured vitality after 7 days of incubation. Histopathology showed ductal adenocarcinoma in four patients, one patient had a tubulovillous adenoma with high grade dysplasia. Results: In our experiment, only one patient sample showed sensitivity for gemcitabine (patient 1). The patient in question was sensitive to all drugs tested. In comparison - patients two and three showed a broad drug resistance. Only a high dose of trametinib was able to inhibit growth in these two patient samples. Both gemcitabine and paclitaxel seemed paradoxally to increase growth in organoids derived from patient 2. Patient 4 showed sensitivity to all drugs tested, except for gemcitabine. The patient had received gemcitabine as a neoadjuvant, and no decreasement of tumour size was seen on CT-scan after gemcitabine treatment. Conclusions: Organoids from different patients differed in their responses to drugs. In the case of one patient we could see that gemcitabine resistance in organoids correlated with lack of clinical response to gemcitabine during neoadjuvant treatment. Results were ready 4 weeks after operation and can potentially be considered when adjuvant therapy begins. Relative vitality after drug treatment in organoids from four different patients

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