Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.784123
Title: Investigating the diagnostic potential of circulating tumour DNA (ctDNA) as a non-invasive liquid biopsy : from research to clinic
Author: Gale, Davina
ISNI:       0000 0004 7969 6898
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Recent advances in oncology have led to the development of targeted therapies, enabling patients to be treated based on their tumour molecular profile. Whilst tumour biopsies are routinely used for profiling, they can be highly invasive, may not fully reflect the heterogeneity present within the tumour mass, or accurately represent the genomic profile as the tumour evolves over time. Recent interest has focussed on the use of circulating tumour DNA (ctDNA) as a non-invasive 'liquid biopsy'. Cell-free ctDNA, released from cancer cells, is highly fragmented, and carries the same genetic modifications present in the originating tumour, so has potential to be an exquisitely specific biomarker. This thesis will focus on research I have performed over the last decade to investigate the diagnostic potential of ctDNA. I assessed the hypothesis that ctDNA is a clinically useful biomarker, able to correlate with disease burden, monitor tumour dynamics, and be used to guide treatment. I developed novel digital PCR and next generation sequencing (NGS) assays for the highly sensitive detection of ctDNA, and led the development and analytical validation of a clinical diagnostic ctDNA test to ISO15189:2012 regulatory standards, which is now being used in the clinic to stratify advanced non-small cell lung cancer patients to treatment. This thesis involves critical analysis of 14 publications that I have co-authored investigating the use of ctDNA in high-grade serous ovarian, breast and lung cancer, and the development of novel methods to improve sensitivity of detection. When I started this work in 2009, very little was known about the clinical relevance of ctDNA. Since this time, work by myself and others has led to an explosion of interest in this area, leading to significant advances in the use of ctDNA for cancer diagnosis, treatment selection, patient monitoring and detection of minimal residual disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.784123  DOI: Not available
Share: