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From data to bench to bedside
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
From data to bench to bedside
SubTitle
therapeutic targets in breast cancer
Identifier
ETD_2887
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056152
Language
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Breast--Cancer--Treatment
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Tamoxifen
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Biochemical markers
Abstract
(type = abstract)
Understanding individualized breast cancer treatment options can help physicians care for their patients by careful selection of personalized therapies. The first steps towards this goal have already been taken by clinicians, with the frequent use of molecular and genetic biomarkers to classify breast cancer into categories which direct treatment. This thesis will propose new therapeutic targets for different breast cancer subtypes, as well as a new set of biomarkers that more efficiently predict hormone resistance in estrogen positive (ER+) breast tumors. A novel methodology for therapeutic target prediction will be proposed, based on a new paradigm called “gene centrality”. In addition to being over-expressed, good therapeutic targets should have a high degree of connectivity in the tumor network. Gene centrality encompasses this concept by measuring the connectivity of genes in a network in which each edge is weighted by the level of over-expression of the target gene. Using this method, a series of high centrality SRC proto-oncogenes (LYN, YES1, HCK, FYN, and LCK) were identified in subsets of Basal-like and HER2+ breast cancers. The hypothesis that YES1 is a therapeutic target in breast cancer was experimentally tested. We found that Basal-like breast tumor cell lines showed a significant decrease in fitness upon silencing the expression of YES1. Another validated therapeutic target in breast cancer is the estrogen receptor ESR1, targeted by drugs such as Tamoxifen. However, a significant fraction (~30%) of ER+ cases doesn’t respond well to this therapy. A novel outlier analysis method was applied to gene expression data from ER+ breast cancer patients to identify genes highly associated with Tamoxifen resistance. These included cell cycle genes as well as several chromosomal amplification sites. In addition to the well known HER2 amplicon on 17q12, we discovered that amplicons in 8q24.3, 8p11.2 and 17q21.33-q25.1 correlate strongly with early distant metastasis and poor long term survival. As independent biomarkers for Tamoxifen resistance, together these chromosomal regions are predictive for ~75% of patients that suffer early disease relapse.
PhysicalDescription
Form
(authority = gmd)
electronic resource
Extent
viii, 112 p. : ill.
InternetMediaType
application/pdf
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text/xml
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Erhan Bilal
Name
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(type = personal)
NamePart
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Bilal
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Erhan
NamePart
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1979-
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author
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Erhan Bilal
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(type = family)
Bhanot
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Gyan
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chair
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Advisory Committee
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Gyan Bhanot
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NamePart
(type = family)
Sengupta
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(type = given)
Anirvan
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internal member
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Advisory Committee
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Anirvan Sengupta
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(ID = NAME-4);
(type = personal)
NamePart
(type = family)
Mischaikow
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(type = given)
Konstantin
Role
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internal member
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Advisory Committee
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Konstantin Mischaikow
Name
(ID = NAME-5);
(type = personal)
NamePart
(type = family)
Ganesan
NamePart
(type = given)
Shridar
Role
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outside member
Affiliation
Advisory Committee
DisplayForm
Shridar Ganesan
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(ID = NAME-2);
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NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
OriginInfo
DateCreated
(qualifier = exact)
2010
DateOther
(qualifier = exact);
(type = degree)
2010-10
Place
PlaceTerm
(type = code)
xx
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T35D8RNF
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Bilal
GivenName
Erhan
Role
Copyright Holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-09-21 16:48:03
AssociatedEntity
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(AUTHORITY = rulib)
Role
Copyright holder
Name
Erhan Bilal
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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(AUTHORITY = rulib)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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Technical
ContentModel
ETD
MimeType
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application/pdf
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application/x-tar
FileSize
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9625600
Checksum
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03023b05c1c4e13c0d79ea18eeaa36a0f3b478f4
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Statistical Profile