J Clin Neurol.  2015 Apr;11(2):172-177. 10.3988/jcn.2015.11.2.172.

Preclinical Assessment of the Anticancer Drug Response of Plexiform Neurofibroma Tissue Using Primary Cultures

Affiliations
  • 1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. w.jiang@uke.de
  • 2Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

BACKGROUND AND PURPOSE
Individualized drug testing for tumors using a strategy analogous to antibiotic tests for infectious diseases would be highly desirable for personalized and individualized cancer care.
METHODS
Primary cultures containing tumor and nontumor stromal cells were utilized in a novel strategy to test drug responses with respect to both efficacy and specificity. The strategy tested in this pilot study was implemented using four primary cultures derived from plexiform neurofibromas. Responses to two cytotoxic drugs (nilotinib and imatinib) were measured by following dose-dependent changes in the proportions of tumor and nontumor cells, determined by staining them with cell-type-specific antibodies. The viability of the cultured cells and the cytotoxic effect of the drugs were also measured using proliferation and cytotoxicity assays.
RESULTS
The total number of cells decreased after the drug treatment, in accordance with the observed reduction in proliferation and increased cytotoxic effect upon incubation with the two anticancer drugs. The proportions of Schwann cells and fibroblasts changed dose-dependently, although the patterns of change varied between the tumor samples (from different sources) and between the two drugs. The highly variable in vitro drug responses probably reflect the large variations in the responses of tumors to therapies between individual patients in vivo.
CONCLUSIONS
These preliminary results suggest that the concept of assessing in vitro drug responses using primary cultures is feasible, but demands the extensive further development of an application for preclinical drug selection and drug discovery.

Keyword

personalized medicine; drug selection; preclinical test; specificity; primary culture; in vitro testing

MeSH Terms

Antibodies
Cells, Cultured
Communicable Diseases
Drug Discovery
Fibroblasts
Humans
Precision Medicine
Neurofibroma, Plexiform*
Pilot Projects
Schwann Cells
Sensitivity and Specificity
Stromal Cells
Antibodies
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