Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for +publisher:"University of North Carolina" +contributor:("Whittle, Martin C."). One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of North Carolina

1. Whittle, Martin C. Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics.

Degree: Pharmacology, 2013, University of North Carolina

Kinases are members of a large dynamic and cooperative signaling network, which senses inhibition of key nodal kinases and induces compensatory responses that offset pharmacological intervention. Combination therapies that target multiple growth- and survival promoting kinases are proving to be a better strategy for successful cancer therapy. What is lacking is the ability to measure whole kinome activity and to assess kinome adaptation and resistance to targeted therapies. We have developed a chemical proteomics approach that couples kinase affinity capture with quantitative mass spectrometry, providing a systems biology platform to profile global kinome activity in cancer cells, GEMM tumors and patient biopsies. Our chemical proteomic approach captures the majority of the expressed kinome estimated by RNA-seq and detects altered kinome activity profiles in response to stimulus or kinase inhibitors. Kinases from all major kinome subfamilies are captured with a large percentage representing the understudied kinome. Applying this technology, we discovered previously undefined activation of tyrosine and serine/threonine kinases in breast cancer cell lines in response to targeted inhibitors against MEK or EGFR that are currently undergoing clinical trials. Combined kinome activity assessment using chemical proteomics and RNAi synthetic lethal screens predicted a specific kinase inhibitor combination therapy. The combination therapy gave apoptosis and tumor regression in a breast cancer GEMM, where single agents were largely ineffective. The relevance of kinome reprogramming to patient triple-negative breast cancer was confirmed by the investigation of MEK inhibitor-treated patient samples from a window trial established in conjunction with GlaxoSmithKline. However, differential kinome responses were observed across intrinsic breast cancer subtypes, suggesting that broader approaches to targeting or preventing kinome reprogramming may be necessary to avert resistance to kinase inhibitor therapies. The findings presented here define a novel approach to determining kinome-based mechanisms of resistance to targeted therapies to suggest novel inhibitor combinations and strategies that may more effectively treat triple-negative breast cancer. Advisors/Committee Members: Whittle, Martin C., Johnson, Gary.

Subjects/Keywords: School of Medicine; Department of Pharmacology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Whittle, M. C. (2013). Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:9ae50bab-4c5d-47ec-a991-f6785a6e367b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Whittle, Martin C. “Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics.” 2013. Thesis, University of North Carolina. Accessed October 30, 2020. https://cdr.lib.unc.edu/record/uuid:9ae50bab-4c5d-47ec-a991-f6785a6e367b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Whittle, Martin C. “Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics.” 2013. Web. 30 Oct 2020.

Vancouver:

Whittle MC. Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2020 Oct 30]. Available from: https://cdr.lib.unc.edu/record/uuid:9ae50bab-4c5d-47ec-a991-f6785a6e367b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Whittle MC. Targeting the Triple-Negative Breast Cancer Kinome with Chemical Proteomics. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:9ae50bab-4c5d-47ec-a991-f6785a6e367b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.