Göteborgs universitets publikationer

Data-driven modeling of combination therapy in oncology

Författare och institution:
Tim Cardilin (Institutionen för matematiska vetenskaper, matematik, Chalmers/GU)
Publikationstyp:
Licentiatavhandling
Förlag:
Chalmers University of Technology
Förlagsort:
Gothenburg
Publiceringsår:
2016
Språk:
engelska
Datum för examination:
2016-10-07
Tidpunkt för examination:
10:15
Lokal:
MVH12, Hörsalsvägen 1
Opponent:
Dr. Philip Gerlee, Mathematical Sciences, Chalmers University of Technology and University of Gothenburg
Sammanfattning (abstract):
This thesis contains two manuscripts: Tumor Static Concentration Curves in Combination Therapy and Extending the Tumor Static Concentration Curve to Exposure - A Combination Therapy Example with Radiation Therapy. There is also an introductory chapter presenting some basic facts necessary to understand the appended manuscripts. The manuscripts share the common goal of developing model-based data-driven tools and techniques to quantitatively assess the effectiveness of anticancer combinations. The first paper presents a dynamical systems model for combination therapy with the anticancer drugs cetuximab and cisplatin. Using a mixed-effects approach the model is shown to adequately describe a preclinical dataset. The model is then analyzed by introducing the Tumor Static Concentration (TSC) curve, a curve of cetuximab-cisplatin concentration pairs all of which, if maintained, result in tumor stasis. The TSC analysis reveals a modest gain from combining the compounds. The variability of the TSC curve across the population is also explored. In the second paper we develop a dynamical systems model for combination therapy with ionizing radiation and a test compound. For this combination we introduce an extension of the TSC curve called the (average) Tumor Static Exposure (TSE) curve based on average, as opposed to pointwise, tumor stasis. The TSE analysis for combinations of radiation and the test compound demonstrates a large synergistic effect.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
NATURVETENSKAP ->
Matematik
NATURVETENSKAP ->
Data- och informationsvetenskap ->
Bioinformatik (beräkningsbiologi)
NATURVETENSKAP ->
Data- och informationsvetenskap ->
Annan data- och informationsvetenskap
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Farmaceutisk vetenskap
Nyckelord:
Oncology, Model-Based Drug Development, Pharmacokinetics/Pharmacodynamics, Nonlinear Mixed-Effects Models, Combination Therapy, Mathematical Modeling
Chalmers styrkeområden:
Livsvetenskaper
Postens nummer:
242187