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Model-based assessm...
Model-based assessment of combination therapies - ranking of radiosensitizing agents in oncology
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- Baaz, Marcus, 1993 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences,Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik (FCC),Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC),Chalmers tekniska högskola,Chalmers University of Technology
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- Cardilin, Tim, 1989 (författare)
- Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik (FCC),Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC)
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Lignet, F. (författare)
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Zimmermann, A. (författare)
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El Bawab, S. (författare)
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Gabrielsson, J. (författare)
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- Jirstrand, Mats, 1968 (författare)
- Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik (FCC),Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC)
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Bmc Cancer. - 1471-2407. ; 23:1
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- Background To increase the chances of finding efficacious anticancer drugs, improve development times and reduce costs, it is of interest to rank test compounds based on their potential for human use as early as possible in the drug development process. In this paper, we present a method for ranking radiosensitizers using preclinical data. Methods We used data from three xenograft mice studies to calibrate a model that accounts for radiation treatment combined with radiosensitizers. A nonlinear mixed effects approach was utilized where between-subject variability and inter-study variability were considered. Using the calibrated model, we ranked three different Ataxia telangiectasia-mutated inhibitors in terms of anticancer activity. The ranking was based on the Tumor Static Exposure (TSE) concept and primarily illustrated through TSE-curves. Results The model described data well and the predicted number of eradicated tumors was in good agreement with experimental data. The efficacy of the radiosensitizers was evaluated for the median individual and the 95% population percentile. Simulations predicted that a total dose of 220 Gy (5 radiation sessions a week for 6 weeks) was required for 95% of tumors to be eradicated when radiation was given alone. When radiation was combined with doses that achieved at least 8 mu g/mL of each radiosensitizer in mouse blood, it was predicted that the radiation dose could be decreased to 50, 65, and 100 Gy, respectively, while maintaining 95% eradication. Conclusions A simulation- based method for calculating TSE-curves was developed, which provides more accurate predictions of tumor eradication than earlier, analytically derived, TSE- curves. The tool we present can potentially be used for radiosensitizer selection before proceeding to subsequent phases of the drug discovery and development process.
Ämnesord
- NATURVETENSKAP -- Matematik (hsv//swe)
- NATURAL SCIENCES -- Mathematics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Radiation therapy
- Combination therapy
- Tumor static exposure
- Non-linear mixed effects
- Inter-study variability
- tumor-growth
- cancer
- radiation
- dynamics
- impact
- chemotherapy
- radiotherapy
- variability
- inhibition
- strategies
- Oncology
- Inter-study variability
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Baaz, Marcus, 19 ...
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Cardilin, Tim, 1 ...
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Lignet, F.
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Zimmermann, A.
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El Bawab, S.
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Gabrielsson, J.
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visa fler...
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Jirstrand, Mats, ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Matematik
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Farmaceutiska ve ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Radiologi och bi ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Bmc Cancer
- Av lärosätet
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Göteborgs universitet
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Chalmers tekniska högskola