Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) remains a global health challenge that affects more than 700,000 people yearly and has a devastating five-year survival rate at <20%. Current standard of care treatment for HCC showed limited efficacy in patients, driving the need for a more effective targeted thera...
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sg-ntu-dr.10356-1609362023-10-02T15:32:57Z Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma Yeo, Joanna Zhen Zhen - School of Biological Sciences Torsten Wustefeld Wustefeldt@gis.a-star.edu.sg Science::Biological sciences Hepatocellular carcinoma (HCC) remains a global health challenge that affects more than 700,000 people yearly and has a devastating five-year survival rate at <20%. Current standard of care treatment for HCC showed limited efficacy in patients, driving the need for a more effective targeted therapy. As the major metabolic hub of the body, the liver undergoes tremendous metabolic reprogramming during tumorigenesis. Such remodelling could result in the activation of new metabolic pathways, creating new adaptative mechanisms or cancer-specific dependencies that could be potentially targeted. To uncover clinically relevant cancer-specific metabolic targets, patient derived HCC models were generated and subjected to a high throughput metabolic screening. This revealed therapeutic vulnerability of a subset of HCC towards NAD metabolism and circadian rhythm related pathways, which are commonly dysregulated pathways in HCC. Understanding the mechanistic underpinning this highly unique and understudied pathway in HCC could have potential implications for novel treatment modalities in HCC. Doctor of Philosophy 2022-08-08T04:50:26Z 2022-08-08T04:50:26Z 2022 Thesis-Doctor of Philosophy Yeo, J. Z. Z. (2022). Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/160936 https://hdl.handle.net/10356/160936 10.32657/10356/160936 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |
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Science::Biological sciences Yeo, Joanna Zhen Zhen Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
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Hepatocellular carcinoma (HCC) remains a global health challenge that affects more than 700,000 people yearly and has a devastating five-year survival rate at <20%. Current standard of care treatment for HCC showed limited efficacy in patients, driving the need for a more effective targeted therapy. As the major metabolic hub of the body, the liver undergoes tremendous metabolic reprogramming during tumorigenesis. Such remodelling could result in the activation of new metabolic pathways, creating new adaptative mechanisms or cancer-specific dependencies that could be potentially targeted. To uncover clinically relevant cancer-specific metabolic targets, patient derived HCC models were generated and subjected to a high throughput metabolic screening. This revealed therapeutic vulnerability of a subset of HCC towards NAD metabolism and circadian rhythm related pathways, which are commonly dysregulated pathways in HCC. Understanding the mechanistic underpinning this highly unique and understudied pathway in HCC could have potential implications for novel treatment modalities in HCC. |
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author_facet |
- Yeo, Joanna Zhen Zhen |
format |
Thesis-Doctor of Philosophy |
author |
Yeo, Joanna Zhen Zhen |
author_sort |
Yeo, Joanna Zhen Zhen |
title |
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
title_short |
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
title_full |
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
title_fullStr |
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
title_full_unstemmed |
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma |
title_sort |
therapeutic targeting of nampt and its associated pathways in hepatocellular carcinoma |
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Nanyang Technological University |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/160936 |
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1779156243449905152 |