title: Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors.
abstract: BACKGROUND
  Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon.
  
  
  METHODS
  We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined.
  
  
  RESULTS
  New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients.
  
  
  CONCLUSIONS
  These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling.
authors.affiliation: Research Group Molecular OncoSurgery, University of Heidelberg, Im Neuenheimer Feld 365, Heidelberg 69120, Germany.
authors.forename: Chengwen
authors.initials: C
authors.lastname: Zhang
authors.forename: Till
authors.initials: T
authors.lastname: Wenger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mattern
authors.forename: Septimia
authors.initials: S
authors.lastname: Ilea
authors.forename: Christian
authors.initials: C
authors.lastname: Frey
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Wolfram
authors.initials: W
authors.lastname: Bodenmüller
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gassler
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Marmé
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Jesco
authors.initials: J
authors.lastname: Pfitzenmaier
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Armin
authors.initials: A
authors.lastname: Kolb
authors.forename: Peter
authors.initials: P
authors.lastname: Büchler
authors.forename: Markus
authors.initials: M
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Werner
authors.initials: W
authors.lastname: Rittgen
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
authors.forename: Hans P
authors.initials: HP
authors.lastname: Rutz
authors.forename: Ingrid
authors.initials: I
authors.lastname: Herr
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy
chemical_list: D005938:Glucocorticoids