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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Main Author: Yeo, Joanna Zhen Zhen
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Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2022
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Online Access:https://hdl.handle.net/10356/160936
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Institution: Nanyang Technological University
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
spellingShingle Science::Biological sciences
Yeo, Joanna Zhen Zhen
Therapeutic targeting of NAMPT and its associated pathways in hepatocellular carcinoma
description 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.
author2 -
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
publisher Nanyang Technological University
publishDate 2022
url https://hdl.handle.net/10356/160936
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