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Metabolic vulnerabilities in clear cell renal cell carcinoma Nathan J Coffey
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Coffey, Nathan J., author.
- Language:
- English
- Subjects (All):
- Biology.
- Molecular biology.
- Genetics.
- Cellular biology.
- Oncology.
- 0306.
- 0307.
- 0369.
- 0379.
- 0992.
- Local Subjects:
- Biology.
- Molecular biology.
- Genetics.
- Cellular biology.
- Oncology.
- 0306.
- 0307.
- 0369.
- 0379.
- 0992.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (237 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Clear cell renal cell carcinoma (ccRCC) is a deadly disease associated with consistent metabolic reprogramming that facilitates its growth and survival in harsh tumor microenvironments. Using a multi-omics approach that consisted of analyzing publicly available RNA-seq, proteomics, metabolomics, and chromosomal copy number alterations from patients with ccRCC, we identified metabolic vulnerabilities that could be leveraged to reduce ccRCC growth in vitro and in vivo using pharmacologic and genetic approaches. In chapter 2, we identified the bile acid biosynthetic enzyme HSD3B7 is essential for clear cell renal cell carcinoma cell survival and can be targeted to induce accumulation of cholesterol-derived oxysterols and apoptotic cell death. In chapter 3, we reveal BCAA transamination sustains ccRCC proliferation in low glutamine conditions and can be targeted in combination with glutaminase inhibition to induce synthetic lethality in ccRCC by reducing glutamate and glutathione levels. Taken together, these discoveries reveal ccRCC has metabolic dependencies that can be targeted to reduce its growth
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Simon, M. Celeste; Arany, Zoltan Pierre; Titchenell, Paul M. Committee members: Wellen, Kathryn E.; Susztak, Katalin; Schug, Zachary
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247980452
- Access Restriction:
- Restricted for use by site license
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