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Understanding the vulnerabilities of tumors : a network-based approach to drug target discovery / by Nadia M. Penrod.

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Author	Penrod, Nadia M.
Title	Understanding the vulnerabilities of tumors : a network-based approach to drug target discovery / by Nadia M. Penrod.
Date	2013
Abstract	The demand for novel molecularly targeted drugs will continue to rise as we make progress toward personalizing cancer treatments to the molecular signatures of individual tumors. While the collection and analysis of genomic data has become routine, one of the biggest challenges facing drug discovery is the identification of potential drug targets and combinations of targets that can be safely and effectively modulated. This is attributable to conventional analysis methods that take a reductionist approach, studying one gene at a time in an effort to identify disease-associated genes as potential drug targets. These approaches, disregard the context-dependent function of genes. More promising approaches, such as network biology, embrace the complexity of biological function by capturing both individual molecular interactions and a global snapshot of how these interactions fit together to create a functional system. Here, we explore coexpression networks as a contextual background for the discovery of novel drug targets and introduce network-based metrics to prioritize genes as potential targets. We apply these methods to coexpression networks generated from ER⁺ breast tumor biopsy data collected during the course of neoadjuvant treatment with the drug letrozole. We show that coexpression captures tumor adaptation to drug treatment, we identify biologically relevant drug targets to guide the development of cancer therapeutics, and we discuss how these metrics can be used to design combination therapy treatment strategies that adapt with the changing tumor phenotype.
Description	xi, 132 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Jason H. Moore, Alan R. Eastman, Angeline S. Andrew, Joel T. Dudley,
College	"Dartmouth Medical School.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1000

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