title: Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer.
abstract: OBJECTIVE
  Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed.
  
  
  METHODS
  Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL.
  
  
  RESULTS
  HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bcl-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wild-type p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC.
  
  
  CONCLUSIONS
  Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Bauer
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Kitrina G
authors.initials: KG
authors.lastname: Cordell
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.forename: Huong H
authors.initials: HH
authors.lastname: Tran
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Steven
authors.initials: S
authors.lastname: Wang
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.forename: Susan G
authors.initials: SG
authors.lastname: Urba
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
authors.forename: Julia
authors.initials: J
authors.lastname: Lee
authors.forename: Kent A
authors.initials: KA
authors.lastname: Griffith
authors.forename: Jeremy M G
authors.initials: JM
authors.lastname: Taylor
authors.forename: Nisha
authors.initials: N
authors.lastname: D'Silva
authors.forename: Shaomeng J
authors.initials: SJ
authors.lastname: Wang
authors.forename: Keith G
authors.initials: KG
authors.lastname: Wolter
authors.forename: Bradley
authors.initials: B
authors.lastname: Henson
authors.forename: Susan G
authors.initials: SG
authors.lastname: Fisher
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D002945:Cisplatin