title: Molecular imaging reveals a role for AKT in resistance to cisplatin for ovarian endometrioid adenocarcinoma.
abstract: OBJECTIVE
  Ovarian cancer is the fifth leading cause of cancer-related deaths among American women. Platinum-based chemotherapy, such as cisplatin, represents the standard-of-care for ovarian cancer. However, toxicity and acquired resistance to cisplatin have proven challenging in the treatment of patients with ovarian cancer.
  
  
  METHODS
  Using a genetically engineered mouse model of ovarian endometrioid adenocarcinoma (OEA) in combination with molecular-imaging technologies, we studied the activation of the AKT serine/threonine kinase in response to long-term cisplatin therapy.
  
  
  RESULTS
  Treatment of cells in culture and tumor-bearing animals with cisplatin resulted in activation of AKT, a key mediator of cell survival. On the basis of these results, we investigated the therapeutic use of AKT inhibition in combination with cisplatin, which resulted in enhanced and prolonged induction of apoptosis and in significantly improved tumor control as compared with either agent alone.
  
  
  CONCLUSIONS
  These results provide an impetus for clinical trials using combination therapy. To facilitate these trials, we also show the use of diffusion-weighted MRI as an imaging biomarker for evaluation of therapeutic efficacy in OEA.
authors.affiliation: Center for Molecular Imaging, Departments of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Hanxiao
authors.initials: H
authors.lastname: Wang
authors.forename: Stefanie
authors.initials: S
authors.lastname: Galbán
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Bowman
authors.forename: Amanda
authors.initials: A
authors.lastname: Witte
authors.forename: Katrin
authors.initials: K
authors.lastname: Vetter
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Galbán
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Cho
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin