Development of pathway-based biomarker in breast cancer and assessment of feasibility of integrating transcriptomics data in electronic health record

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Title Development of pathway-based biomarker in breast cancer and assessment of feasibility of integrating transcriptomics data in electronic health record
Publication Type dissertation
School or College School of Medicine
Department Biomedical Informatics
Author Rahman, Mumtahena
Date 2015-12
Description Despite the advancements in therapies, next-generation sequencing, and our knowledge, breast cancer is claiming hundreds of thousands of lives around the world every year. We have therapy options that work for only a fraction of the population due to the heterogeneity of the disease. It is still overwhelmingly challenging to match a patient with the appropriate available therapy for the optimal outcome. This dissertation work focuses on using biomedical informatics approaches to development of pathwaybased biomarkers to predict personalized drug response in breast cancer and assessment of feasibility integrating such biomarkers in current electronic health records to better implement genomics-based personalized medicine. The uncontrolled proliferation in breast cancer is frequently driven by HER2/PI3K/AKT/mTOR pathway. In this pathway, the AKT node plays an important role in controlling the signal transduction. In normal breast cells, the proliferation of cells is tightly maintained at a stable rate via AKT. However, in cancer, the balance is disrupted by amplification of the upstream growth factor receptors (GFR) such as HER2, IGF1R and/or deleterious mutations in PTEN, PI3KCA. Overexpression of AKT leads to increased proliferation and decreased apoptosis and autophagy, leading to cancer. Often these known amplifications and the mutation status associated with the disease progression are used as biomarkers for determining targeting therapies. However, downstream known or unknown mutations and activations in the pathways, crosstalk iv between the pathways, can make the targeted therapies ineffective. For example, one third of HER2 amplified breast cancer patients do not respond to HER2-targeting therapies such as trastuzumab, possibly due to downstream PTEN loss of mutation or PIK3CA mutations. To identify pathway aberration with better sensitivity and specificity, I first developed gene-expression-based pathway biomarkers that can identify the deregulation status of the pathway activation status in the sample of interest. Second, I developed drug response prediction models primarily based on the pathway activity, breast cancer subtype, proteomics and mutation data. Third, I assessed the feasibility of including gene expression data or transcriptomics data in current electronic health record so that we can implement such biomarkers in routine clinical care.
Type Text
Publisher University of Utah
Subject Bioinformatics; Information science
Subject MESH Breast Neoplasms; Biomarkers, Tumor; Electronic Health Records; Precision Medicine; Medical Informatics Applications; Gene Expression Profiling; Signal Transduction; Feasibility Studies; Sensitivity and Specificity; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Genomics; Phenotype; Receptors, Estrogen; Receptors, Progesterone; Receptor, ErbB-2; Systematized Nomenclature of Medicine; Vocabulary, Controlled; Programming Languages
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Development of Pathway-Based Biomarker in Breast Cancer and Assessment of Feasibility of Integrating Transcriptomics Data in Electronic Health Record
Rights Management Copyright © Mumtahena Rahman 2015
Format application/pdf
Format Medium application/pdf
Format Extent 12,735,774 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s64n2cvt
Setname ir_etd
ID 197342
Reference URL https://collections.lib.utah.edu/ark:/87278/s64n2cvt
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