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Article

Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro

1
Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany
2
Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, University Hospital Düsseldorf, 40225 Düsseldorf, Germany
3
Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
4
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
5
IUF—Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany
6
Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany
7
Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(12), 2689; https://doi.org/10.3390/cells9122689
Received: 16 November 2020 / Revised: 8 December 2020 / Accepted: 9 December 2020 / Published: 15 December 2020
(This article belongs to the Special Issue Molecular Biology in Glioblastoma Multiforme Treatment)
In cancer pharmacology, a drug candidate’s therapeutic potential is typically expressed as its ability to suppress cell growth. Different methods in assessing the cell phenotype and calculating the drug effect have been established. However, inconsistencies in drug response outcomes have been reported, and it is still unclear whether and to what extent the choice of data post-processing methods is responsible for that. Studies that systematically examine these questions are rare. Here, we compare three established calculation methods on a collection of nine in vitro models of glioblastoma, exposed to a library of 231 clinical drugs. The therapeutic potential of the drugs is determined on the growth curves, using growth inhibition 50% (GI50) and point-of-departure (PoD) as the criteria. An effect is detected on 36% of the drugs when relying on GI50 and on 27% when using PoD. For the area under the curve (AUC), a threshold of 9.5 or 10 could be set to discriminate between the drugs with and without an effect. GI50, PoD, and AUC are highly correlated. The ranking of substances by different criteria varies somewhat, but the group of the top 20 substances according to one criterion typically includes 17–19 top candidates according to another. In addition to generating preclinical values with high clinical potential, we present off-target appreciation of top substance predictions by interrogating the drug response data of non-cancer cells in our calculation technology. View Full-Text
Keywords: glioblastoma; in vitro pharmacology; quantification; drug response; mathematical modeling; off-target risk glioblastoma; in vitro pharmacology; quantification; drug response; mathematical modeling; off-target risk
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MDPI and ACS Style

Fischer, I.; Nickel, A.-C.; Qin, N.; Taban, K.; Pauck, D.; Steiger, H.-J.; Kamp, M.; Muhammad, S.; Hänggi, D.; Fritsche, E.; Remke, M.; Kahlert, U.D. Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro. Cells 2020, 9, 2689. https://doi.org/10.3390/cells9122689

AMA Style

Fischer I, Nickel A-C, Qin N, Taban K, Pauck D, Steiger H-J, Kamp M, Muhammad S, Hänggi D, Fritsche E, Remke M, Kahlert UD. Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro. Cells. 2020; 9(12):2689. https://doi.org/10.3390/cells9122689

Chicago/Turabian Style

Fischer, Igor, Ann-Christin Nickel, Nan Qin, Kübra Taban, David Pauck, Hans-Jakob Steiger, Marcel Kamp, Sajjad Muhammad, Daniel Hänggi, Ellen Fritsche, Marc Remke, and Ulf D. Kahlert 2020. "Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro" Cells 9, no. 12: 2689. https://doi.org/10.3390/cells9122689

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