HuR modulates gemcitabine efficacy: new perspectives in pancreatic cancer treatment.
EVALUATION OF: Costantino CL, Witkiewicz AK, Kuwano Y et al. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res. 69, 4567-4572 (2009). Gemcitabine has been the standard of care for pancreatic cancer for a decade but is only effective in some patients. As a prodrug, gemcitabine is activated by different protein kinases. The deoxycytidine kinase (dCK) is the first step of intracellular activation. We review the study by Costantino and colleagues, evaluating the consequence of modulating Hu antigen R (HuR), a stress response protein, on dCK expression and the correlation between HuR expression levels and pancreatic cancer outcome. This study demonstrates that dCK protein concentration levels were regulated by HuR and that a high cytoplasmic HuR level was associated with a sevenfold decreased risk of mortality after resection of pancreatic adenocarcinoma and gemcitabine therapy.
Maréchal
Raphaël
R
Department of Gastroenterology and Pancreatology, Gastrointestinal Cancer Unit Erasme University Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium. rmarecha@ulb.ac.be
Van Laethem
Jean-Luc
JL
D000954:Antigens, Surface / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000235:genetics; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011355:Prodrugs; D016601:RNA-Binding Proteins / Q000235:genetics; D016896:Treatment Outcome; D000093542:Gemcitabine
D000954:Antigens, Surface; D000964:Antimetabolites, Antineoplastic; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D011355:Prodrugs; D016601:RNA-Binding Proteins; D003841:Deoxycytidine; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine