Small-molecule inhibition of general transcriptional regulators in cancer
Name
969341273-MIT.pdf
Description
Full printable version
Size
10.9 MB
Format
Adobe PDF
Checksum (MD5)
55f40b8156ff2292193cbf9f8a0fe24e
Author(s)
Reddy, Jessica
Advisor(s)
Richard A. Young.
Date Issued
2016
Publisher
Massachusetts Institute of Technology
Abstract
Transcription is frequently deregulated in cancer, but targeting of transcriptional processes for cancer therapy has thus far been limited to nuclear receptors. Recent studies, however, have suggested that inhibitors of various general transcriptional regulators can be used in cancer therapy because expression of some oncogenes is disproportionately sensitivity to these inhibitors. Here, I describe the cellular and molecular effects of inhibiting a general transcriptional regulator, CDK7, in T-cell acute lymphoblastic leukemia (T-ALL) cells. Because tumor cells commonly evolve resistance to individual therapies, I have also investigated the potentially synergistic effects of combining two compounds that target transcriptional regulators - the CDK7-inhibitor THZ1 and the BRD4-inhibitor JQ1 - and suggest a model describing the molecular basis of the synergistic effects I observed. My research provides insight into the effects of these inhibitors of general transcriptional regulators on tumor cell behavior and gene expression programs.
Description
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
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