Targeting TYMS as a Therapeutic Strategy for Aggressive Prostate Cancers
Abstract/Contents
- Abstract
- In the modern-day United States, prostate cancer (PC) remains the most common non-skin cancer in men. While the 5-year survival for localized prostate cancer is greater than 99%, patients with aggressive, metastatic prostate cancer subtypes experience worse prognostics and a 5-year survival of only 31%. This suggests that aggressive, metastatic prostate cancer subtypes are responsible for the majority of prostate cancer-driven deaths and underscores the need to develop novel therapies for these aggressive PCs. The DNA replication and repair pathway is a common target in cancer therapies since DNA de-regulation is a well-identified cancer hallmark. Thymidylate synthase (TYMS), an enzyme that is an important component of DNA synthesis, replication, and repair due to its synthesis of thymidylate, has been identified as a potential therapeutic target for aggressive PCs since TYMS is highly expressed in invasive PC subtypes and exert anti-cancer activities in vitro and in vivo. Our result indicates a positive association between TYMS expression and PC progression since TYMS is elevated in metastatic patient tumors relative to benign and localized samples, and TYMS is also up-regulated in AR-independent castration resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) relative to localized and normal prostate tissues in patient tissue microarray (TMA). Results from in vitro cell viability and colony formation assays also indicate that TYMS inhibition exerts anti-cancer activities in the reduction of PC cell viability, colony-forming ability, and tumor growth. Thus, we propose TYMS as a novel therapeutic target against metastatic, invasive PC subtypes.
Description
| Type of resource | text |
|---|---|
| Date modified | December 5, 2022 |
| Publication date | July 28, 2022; May 13, 2022 |
Creators/Contributors
| Author | Shen, Michelle |
|---|---|
| Thesis advisor | Stoyanova, Tanya |
| Thesis advisor | Bintu, Lacramioara |
| Thesis advisor | Liu, Shiqin |
| Degree granting institution | Stanford University |
| Department | Department of Bioengineering |
Subjects
| Subject | Prostate > Cancer > Treatment |
|---|---|
| Subject | Raltitrexed |
| Subject | Pemetrexed |
| Subject | Thymidylate synthase |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 4.0 International license (CC BY-NC).
Preferred citation
- Preferred citation
- Shen, M. (2022). Targeting TYMS as a Therapeutic Strategy for Aggressive Prostate Cancers. Stanford Digital Repository. Available at https://purl.stanford.edu/rw873vp5865
Collection
Undergraduate Theses, School of Engineering
View other items in this collection in SearchWorksContact information
- Contact
- ms0122ms@stanford.edu
Also listed in
Loading usage metrics...