title: Gemcitabine chemoresistance in pancreatic cancer: molecular mechanisms and potential solutions.
abstract: Ductal pancreatic adenocarcinoma is associated with a very poor prognosis and most patients are given palliative care. Chemotherapy in the form of gemcitabine has been found to reduce disease-related pain, and the otherwise frequently occurring weight changes, to increase Karnofsky performance status and quality of life and has also resulted in a modest improvement in survival time. The intracellular uptake of gemcitabine is dependent on nucleoside transporters, predominantly human equilibrative nucleoside transporter-1 (hENT-1), which is over-expressed in human pancreatic adenocarcinoma cells. Cellular resistance to gemcitabine can be intrinsic or acquired during gemcitabine treatment. One of the mechanisms is a decrease in hENT-1 expression. Modifications of gemcitabine not rendering it dependent on the nucleoside transporter may be a successful future mode of chemotherapy treatment, and determination of the nucleoside receptor status at the time of diagnosis could potentially also contribute to a more targeted therapy in the future.
authors.affiliation: Department of Surgery, Clinical Sciences Lund, Lund University Hospital, Sweden. roland.andersson@med.lu.se
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
authors.forename: Ursula
authors.initials: U
authors.lastname: Aho
authors.forename: Bo I
authors.initials: BI
authors.lastname: Nilsson
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Marçal
authors.initials: M
authors.lastname: Pastor-Anglada
authors.forename: Wenche
authors.initials: W
authors.lastname: Rasch
authors.forename: Marit L
authors.initials: ML
authors.lastname: Sandvold
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D010166:Palliative Care / Q000379:methods; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine