Characterizing treatment induced alterations of the tumor microenvironment towards optimizing therapeutic regimens in cancer

dc.contributor.advisorYankeelov, Thomas E.
dc.contributor.committeeMemberBrock, Amy
dc.contributor.committeeMemberSorace, Anna G
dc.contributor.committeeMemberTunnell, James W
dc.contributor.committeeMemberVirostko, Jack
dc.creatorBloom, Meghan Jean
dc.date.accessioned2020-05-22T20:29:23Z
dc.date.available2020-05-22T20:29:23Z
dc.date.created2019-12
dc.date.issued2020-03-26
dc.date.submittedDecember 2019
dc.date.updated2020-05-22T20:29:23Z
dc.description.abstractIt is well recognized that the tumor microenvironment plays a key role in cancer initiation, progression, and response to treatment. Therapies targeted towards the tumor microenvironment are being introduced in the clinic to be administered alongside chemotherapy and radiation, however, not every patient responds to treatment. The purpose of this dissertation is to characterize modulation of the tumor microenvironment induced by targeted therapies, and build a better understanding of how to exploit these alterations to increase efficacy of developing combination treatments. Our objective is addressed in three parts. First, we quantified temporal alterations in nuclear factor kappa B signaling and downstream gene expression to a small-molecule pathway inhibitor and demonstrated the complexity of altering pathway dynamics for therapeutic gain. Secondly, we characterized changes in innate immune cell infiltration in human epidermal growth factor receptor 2 positive (HER2+) breast cancer after targeted antibody treatment and identified mechanisms of vascular alterations and windows of reduced immune suppression. Lastly, we quantified the effects of radiation and targeted antibody therapy in HER2+ breast cancer and elucidated a potential to reduce radiation dose in this combination regimen. Collectively, the results presented provide valuable insight of how the tumor microenvironment can dictate treatment response and the potential to modulate the tumor microenvironment to enhance therapeutic efficacy
dc.description.departmentBiomedical Engineering
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152/81347
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/8355
dc.language.isoen
dc.subjectTrastuzumab
dc.subjectHER2
dc.subjectNuclear factor kappa B
dc.titleCharacterizing treatment induced alterations of the tumor microenvironment towards optimizing therapeutic regimens in cancer
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBiomedical Engineering
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
BLOOM-DISSERTATION-2019.pdf
Size:
4.01 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
4.45 KB
Format:
Plain Text
Description:
No Thumbnail Available
Name:
LICENSE.txt
Size:
1.84 KB
Format:
Plain Text
Description: