gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Identification of the most effective drugs for the individual patient tumor using a 3D sensitivity assay

Meeting Abstract

  • Laura Rava - LMU München, Chirurgische Klinik-Großhadern, Klinische Forschung Chirurgie, H02-312, München
  • Karoline Weiler - LMU München, Chirurgische Klinik-Großhadern, Klinische Forschung Chirurgie, H02-312, München
  • Karl-Walter Jauch - Universitätsklinikum der LMU München-Großhadern, Chirurgische Klinik und Poliklinik, München
  • Ilona Funke - LMU München, Chirurgische Klinik-Großhadern, Klinische Forschung Chirurgie, H02-312, München
  • Barbara Mayer - SpheroTec GmbH, Diagnostics, Martinsried

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch354

DOI: 10.3205/11dgch354, URN: urn:nbn:de:0183-11dgch3545

Published: May 20, 2011

© 2011 Rava et al.
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Outline

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Introduction: Despite chemotherapy, progression rate in CRC is high. Thus, identification of the most effective therapy before starting clinical treatment is an important goal. In the present study the most relevant drugs for the individual cancer patient were identified using a tumor biologically relevant 3D sensitivity assay

Materials and methods: Fresh tumor samples from 25 CRC patients were used to prepare heterotypic spheroids according to the SpheroTec microtumor technology. Cellular composition of the spheroids was analyzed using cell type specific biomarkers. Spheroids were treated with chemotherapeutic and molecular drugs in different combinations, concentrations and time periods. Therapeutic impact on both epithelial cells and leukocytes was measured by FACS analysis

Results: In the traditional 2D chemosensitivity test cell vitality is lost up to 40% within 96 hours. Contrary, in heterotypic spheroids cell survival is upregulated up to 25%. In addition, spheroids closely reflect the biology of the parental tumor, including drugable target expression, chemoresistance and immune cell status. All but one spheroid models showed a higher portion of tumor cells compared to leukocytes (E:T, 1:2 up to 1: 20). Testing standard chemotherapy, i.e. 5-FU and Oxaliplatin (FO), as well as 5-FU and Irinotecan (FI), in 42% of the tumor spheroids FI had a stronger impact on tumor cells compared to FO, while the opposite was found in 16.7 % of the spheroid samples. Additional treatment with Cetuximab (C) revealed a stronger effect in combination with FO (58%) compared to FI (25%), showing dose and time dependency. Compared to the tumor cells, leukocytes showed a stronger reaction to chemotherapy and were most susceptible for Oxaliplatin-based treatment (FO: 50%, FI: 17%). Again, the effect was increased by combination with Cetuximab.

Conclusion: Identification of the most effective drugs before starting therapy represents an important strategy in the treatment management of the individual cancer patient. Using the 3D microtumor sensitivity assay allows drug profiling on both tumor and stromal cells.