Change search
ReferencesLink to record
Permanent link

Direct link
Differentially Regulated pathways of Potential Importance for Treatment Response and Cardiac Toxicity after Administration of Doxorubicine to BC Patients
Norwegian University of Science and Technology, Faculty of Natural Sciences and Technology, Department of Biotechnology.
2012 (English)MasteroppgaveStudent thesis
Abstract [en]

Doxorubicin is a topoisomerase-targeting anthracycline that is one of the most effective anticancer drugs currently known. However, its clinical use is restricted by cardiotoxicity and the development of drug resistance. The main goal of this thesis has been to increase the knowledge of doxorubicin mechanism in addition to evaluate if predictive biomarkers for doxorubicin response could be identified. A total of 128 tumor samples collected from breast cancer patients before and after neoadjuvant treatment with doxorubicin were studied. mRNA expression level in tumor tissue was assessed using whole-genome mRNA microarray analysis (Agilent Human GE 4x44K microarray). More than 5000 genes were found to be up- and down regulated following doxorubicin treatment. The molecular and cellular functions as well as canonical pathways found to be enriched in the list of genes up regulated after doxorubicin exposure were involved in among other cardiovascular system development and function, cellular movement and immune responses. p53 was found to be the transcription factor regulating the highest number of target molecules within the list of up regulated genes. RNA processing, splicing and translation were shown to be overrepresented in the list of down regulated genes. The association between doxorubicin response and changes in gene expression revealed several genes such as CTGF, ITGB4 and IGF1 to be up regulated in the samples collected from patients characterized with a partial response to doxorubicin compared to those with minimal change and/or stable disease following treatment. In addition, the gene expression profiles between samples having wild type compared to mutated TP53 were studied, and a lower induction of expression were found for several genes such as FGF9 and COL11A2 in the samples having a mutated p53. This study showed that the gene expression profile in breast cancer tumors is altered as a response to doxorubicin exposure. Identifying genes significantly altered after therapy and associate their change with response to treatment may help identify the subgroup of patients benefitting from doxorubicin treatment. Patients with little or no effect of treatment could receive alternative therapy and be spared unnecessary treatment and risk of side effects.

Place, publisher, year, edition, pages
Institutt for bioteknologi , 2012. , 104 p.
Keyword [no]
ntnudaim:6939, MBIOT5 Bioteknologi (5 årig), Molekylærbiologi
URN: urn:nbn:no:ntnu:diva-18364Local ID: ntnudaim:6939OAI: diva2:565866
Available from: 2012-11-08 Created: 2012-11-08

Open Access in DiVA

fulltext(2284 kB)279 downloads
File information
File name FULLTEXT01.pdfFile size 2284 kBChecksum SHA-512
Type fulltextMimetype application/pdf
cover(184 kB)52 downloads
File information
File name COVER01.pdfFile size 184 kBChecksum SHA-512
Type coverMimetype application/pdf

By organisation
Department of Biotechnology

Search outside of DiVA

GoogleGoogle Scholar
Total: 279 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 41 hits
ReferencesLink to record
Permanent link

Direct link