SpheroTest in klinischen Studien bei Brustkrebs

Bei der Studie „SpheroNeo“ haben die Wissenschaftler die Vorhersagekraft von Spherotest mit den tatsächlichen Ergebnissen einer Behandlung von Brustkrebspatientinnen verglichen. Dabei handelte es sich um Frauen, die sich aufgrund ihres Krankheitsstadiums einer medikamentösen Behandlung vor der Operation unterzogen haben („neoadjuvante Therapie“).

Die Auswertung ergab eine starke Prädiktivität (Vorhersagekraft) des Spherotests von über 95% für den individuellen Patienten die optimale Therapie zu identifizieren.
Die Chance auf Tumorfreiheit nach der wie geplant applizierten neoadjuvanten Therapie mit dem von SpheroTest identifizierten Medikament verdoppelt sich auf über 52%.

Die Originalpublikation in BMC Cancer finden Sie hier

Wir danken den zertifizierten Brustkrebszentren, die uns unterstützen:

Brustzentrum der LMU München
Brustzentrum der TU München
Brustzentrum am Klinikum Landshut
Brustzentrum Starnberg
Brustzentrum Süd am Klinikum Harlaching des Städtischen Klinikum München
Rinecker Klinik München



Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy—the SpheroNEO study.
Halfter K1, Ditsch N2, Kolberg HC3, Fischer H4, Hauzenberger T5, von Koch FE6, Bauerfeind I7, von Minckwitz G8, Funke I9, Crispin A10, Mayer B11,12; Behalf of the SpheroNEO Study Group.
Author information
Abstract
BACKGROUND:
Aim of this prospective study was to predict response to neoadjuvant therapy in breast cancer patients using an in vitro breast cancer spheroid model.
METHODS:
Three-dimensional spheroids were directly generated from fresh breast tumor biopsies of 78 patients eligible for neoadjuvant therapy. Cell survival was measured after in vitro exposure to the equivalent therapeutic agents in the breast cancer spheroid model. Treatment results in vitro were correlated with pathological complete response (pCR, i.e. ypT0 ypN0) determined at surgery.
RESULTS:
A mean cell survival of 21.8 % was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8 % in 56 patients without pCR (P = .001). The area under the receiver operator characteristic curve to predict pCR was 0.86 (95 % CI: 0.77 to 0.96) for cell survival in vitro compared to 0.80 (95 % CI: 0.70 to 0.90) for a combined model of conventional factors (hormone- and HER2 receptor, and age). A cutoff at 35 % cell survival for the spheroid model was proposed. Out of the 32 patients with values below this threshold, 21 patients (65.6 %) and one patient (2.2 %) with a cell survival greater than 35 % achieved pCR respectively; (sensitivity 95.5 % (95 % CI: 0.86 to 1.00); specificity 80.4 % (95 % CI: 0.70 to 0.91)). Extent of residual disease positively correlated with increased cell survival (P = .021).
CONCLUSION:
The breast cancer spheroid model proved to be a highly sensitive and specific predictor for pCR after neoadjuvant chemotherapy in breast cancer patients.



Impact of the spheroid model complexity on drug response.
Hoffmann OI1, Ilmberger C2, Magosch S3, Joka M4, Jauch KW5, Mayer B6.
Author information
Abstract
Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening models with different complexity. Tumor cell line spheroids were generated from the cell lines Caco-2, DLD-1, COLO 205, HT-29 and HCT-116, and treated with clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) and the molecular drugs Cetuximab, Trastuzumab, Vorinostat and Everolimus. Treatment results were compared with spheroids originated from tumor cell lines (Caco-2, DLD-1) co-cultured with stromal cells (PBMCs, cancer-associated fibroblasts of colorectal origin) and spheroids directly prepared from colon cancer tissues. Different microenvironment compositions altered the tumor cell line spheroid response patterns. Adding PBMCs increased resistance to FO treatment by 10-15% in Caco-2 and DLD-1 spheroids but decreased resistance to FI by 16% in DLD-1 spheroids. Fibroblast co-cultures decreased resistance to FI in Caco-2 spheroids by 38% but had no impact on FO. Treatment of colon cancer tissue spheroids revealed three distinct response pattern subgroups not detectable in 3D cell lines models. The cancer tissue spheroid model mimics both tumor characteristics and the stromal microenvironment and therefore is an invaluable screening model for pharmaceutical drug development.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
KEYWORDS:
Cancer cell line; Drug screening; Human tumor tissue; Spheroid model

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