Cargando…

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

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 report...

Descripción completa

Detalles Bibliográficos
Autores principales: Fischer, Igor, Nickel, Ann-Christin, Qin, Nan, Taban, Kübra, Pauck, David, Steiger, Hans-Jakob, Kamp, Marcel, Muhammad, Sajjad, Hänggi, Daniel, Fritsche, Ellen, Remke, Marc, Kahlert, Ulf Dietrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765228/
https://www.ncbi.nlm.nih.gov/pubmed/33333810
http://dx.doi.org/10.3390/cells9122689
_version_ 1783628442624851968
author Fischer, Igor
Nickel, Ann-Christin
Qin, Nan
Taban, Kübra
Pauck, David
Steiger, Hans-Jakob
Kamp, Marcel
Muhammad, Sajjad
Hänggi, Daniel
Fritsche, Ellen
Remke, Marc
Kahlert, Ulf Dietrich
author_facet Fischer, Igor
Nickel, Ann-Christin
Qin, Nan
Taban, Kübra
Pauck, David
Steiger, Hans-Jakob
Kamp, Marcel
Muhammad, Sajjad
Hänggi, Daniel
Fritsche, Ellen
Remke, Marc
Kahlert, Ulf Dietrich
author_sort Fischer, Igor
collection PubMed
description 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% (GI [Formula: see text]) and point-of-departure (PoD) as the criteria. An effect is detected on 36% of the drugs when relying on GI [Formula: see text] 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. GI [Formula: see text] , 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.
format Online
Article
Text
id pubmed-7765228
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77652282020-12-27 Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro Fischer, Igor Nickel, Ann-Christin Qin, Nan Taban, Kübra Pauck, David Steiger, Hans-Jakob Kamp, Marcel Muhammad, Sajjad Hänggi, Daniel Fritsche, Ellen Remke, Marc Kahlert, Ulf Dietrich Cells Article 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% (GI [Formula: see text]) and point-of-departure (PoD) as the criteria. An effect is detected on 36% of the drugs when relying on GI [Formula: see text] 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. GI [Formula: see text] , 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. MDPI 2020-12-15 /pmc/articles/PMC7765228/ /pubmed/33333810 http://dx.doi.org/10.3390/cells9122689 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fischer, Igor
Nickel, Ann-Christin
Qin, Nan
Taban, Kübra
Pauck, David
Steiger, Hans-Jakob
Kamp, Marcel
Muhammad, Sajjad
Hänggi, Daniel
Fritsche, Ellen
Remke, Marc
Kahlert, Ulf Dietrich
Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title_full Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title_fullStr Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title_full_unstemmed Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title_short Different Calculation Strategies Are Congruent in Determining Chemotherapy Resistance of Brain Tumors In Vitro
title_sort different calculation strategies are congruent in determining chemotherapy resistance of brain tumors in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765228/
https://www.ncbi.nlm.nih.gov/pubmed/33333810
http://dx.doi.org/10.3390/cells9122689
work_keys_str_mv AT fischerigor differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT nickelannchristin differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT qinnan differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT tabankubra differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT pauckdavid differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT steigerhansjakob differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT kampmarcel differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT muhammadsajjad differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT hanggidaniel differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT fritscheellen differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT remkemarc differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro
AT kahlertulfdietrich differentcalculationstrategiesarecongruentindeterminingchemotherapyresistanceofbraintumorsinvitro