title: Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields.
abstract: OBJECTIVE
  Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer.
  
  
  METHODS
  The effect of TTFields in vitro was assessed using cell counts, clonogenic assays, cell cycle analysis and analysis of mitotic figures. The effect in vivo effect was studied in the PC1-0 hamster pancreatic cancer model.
  
  
  RESULTS
  Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy.
  
  
  CONCLUSIONS
  These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer.
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Giladi
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Schneiderman
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Porat
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Mijal
authors.initials: M
authors.lastname: Munster
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Aviran
authors.initials: A
authors.lastname: Itzhaki
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mordechovich
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Cahal
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Eilon D
authors.initials: ED
authors.lastname: Kirson
authors.affiliation: Novocure Ltd., Switzerland.
authors.forename: Uri
authors.initials: U
authors.lastname: Weinberg
authors.affiliation: Novocure Ltd., Haifa, Israel. Electronic address: yoram@novocure.com.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Palti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D003131:Combined Modality Therapy; D006224:Cricetinae; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004560:Electricity; D006801:Humans; D008297:Male; D008647:Mesocricetus; D008938:Mitosis / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016896:Treatment Outcome; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Anti-mitotic; Cell volume; Clonogenic assay; TTFields