Evaluating metabolism in human renal cancer using novel surgical models
type: CreativeWork
description: Within the last two decades, there has been increasing recognition of the pivotal roles of metabolic reprogramming in cancers. Indeed, this evidence has cumulated in the establishment of dysregulated metabolism as a contemporary hallmark of cancer. Metabolomics has been vital to define the metabolic landscape of cancers. This technique allows the simultaneous analyses of hundreds of metabolites present within a system, capturing the downstream interaction between the genome and environment. Renal cell carcinomas (RCC) are increasingly recognised as metabolically-driven types of cancers. This reprogramming of metabolism in RCC has been shown to have a causal role in tumorigenesis, progression, and aggressive disease behaviour. However, the majority of studies in RCC metabolism use conventional metabolomics techniques that provide only a static ‘snapshot’ of cellular metabolism, with limited inferences possible on dysregulated pathway activity. To overcome these limitations, isotopic tracer studies have been recently employed to capture these dynamic processes and enable tracking of nutrient utilisation in cells, thereby permitting the identification of cancer-specific pathway activities, for translation into the clinical setting. These advanced techniques and approaches to study metabolism *in vivo*, in patients have yet to be widely established in RCC and furthermore, there is a lack of clinically relevant models of RCC metabolism locally. The aim of this thesis was to develop novel models of RCC to evaluate metabolism using isotopic tracer studies. In this thesis, I established isotopic tracer studies *in vivo* in surgical patients with RCC. Using a multiomics approach, I characterised the metabolic phenotypes of these tumours and for the first time, evidenced the suppression of gluconeogenesis *in vivo*. Secondly, by developing a novel *in situ* tissue sampling method, I demonstrated the profound impact of ischaemia, a variable commonly associated with conventiona…
abstract: Within the last two decades, there has been increasing recognition of the pivotal roles of metabolic reprogramming in cancers. Indeed, this evidence has cumulated in the establishment of dysregulated metabolism as a contemporary hallmark of cancer. Metabolomics has been vital to define the metabolic landscape of cancers. This technique allows the simultaneous analyses of hundreds of metabolites present within a system, capturing the downstream interaction between the genome and environment. Renal cell carcinomas (RCC) are increasingly recognised as metabolically-driven types of cancers. This reprogramming of metabolism in RCC has been shown to have a causal role in tumorigenesis, progression, and aggressive disease behaviour. However, the majority of studies in RCC metabolism use conventional metabolomics techniques that provide only a static ‘snapshot’ of cellular metabolism, with limited inferences possible on dysregulated pathway activity. To overcome these limitations, isotopic tracer studies have been recently employed to capture these dynamic processes and enable tracking of nutrient utilisation in cells, thereby permitting the identification of cancer-specific pathway activities, for translation into the clinical setting. These advanced techniques and approaches to study metabolism *in vivo*, in patients have yet to be widely established in RCC and furthermore, there is a lack of clinically relevant models of RCC metabolism locally. The aim of this thesis was to develop novel models of RCC to evaluate metabolism using isotopic tracer studies. In this thesis, I established isotopic tracer studies *in vivo* in surgical patients with RCC. Using a multiomics approach, I characterised the metabolic phenotypes of these tumours and for the first time, evidenced the suppression of gluconeogenesis *in vivo*. Secondly, by developing a novel *in situ* tissue sampling method, I demonstrated the profound impact of ischaemia, a variable commonly associated with conventiona…
author: Yong, Cissy
language: eng
keywords: 13carbon metabolic tracing, cancer metabolism, isotopic tracer studies, renal cancer
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/b84dd36c-f7f3-450b-8180-828bc81d725a/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-04-27
date modified: 2026-07-22T22:24:28Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.101965