title: Overcoming nucleoside analog chemoresistance of pancreatic cancer: a therapeutic challenge.
abstract: Clinical refractoriness to nucleoside analogs (e.g., gemcitabine, capecitabine) is a major scientific problem and is one of the main reasons underlying the extremely poor prognostic state of pancreatic cancer. The drugs' effects are suboptimal partly due to cellular mechanisms limiting their transport, activation, and overall efficacy. Nonetheless, novel therapeutic approaches are presently under study to circumvent nucleoside analog resistance in pancreatic cancer. With these new approaches come additional challenges to be addressed. This review describes the determinants of chemoresistance in the gemcitabine cytotoxicity pathways, provides an overview of investigational approaches for overcoming chemoresistance, and discusses new challenges presented. Understanding the future directions of the field may assist in the successful development of novel treatment strategies for enhancing chemotherapeutic efficacy in pancreatic cancer.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Hung
authors.forename: Hardik R
authors.initials: HR
authors.lastname: Mody
authors.forename: Rajgopal
authors.initials: R
authors.lastname: Govindarajan
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000069287:Capecitabine; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine