Immune checkpoint inhibitors have revolutionised the treatment of advanced cancer, leading to durable tumour shrinkage across multiple cancer types. However, response is only seen in a subset of patients and immune related adverse events that mimic autoimmune disease may occur, irrespective of response. There is an urgent need for biomarkers that predict response and toxicity to determine which patients will benefit most from these potentially toxic therapies. The continuous release of tumour microenvironment derived genomic and proteomic material into the circulation has the potential to be used as a biomarker of response and survival. Therefore, its role in personalised therapy, prognostication and predicting immune related adverse events warrants investigation.
Table of Contents
Chapter 1: Melanoma pathogenesis, staging and systemic therapy -- Chapter 2: Biomarkers in Advanced Melanoma: Particular focus on prognosis and immunotherapy response -- Chapter 3: Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients -- Chapter 4: Metastasis-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma -- Chapter 5: Circulating tumour DNA predicts response in anti-PD1 antibodies in metastatic melanoma -- Chapter 6: Association between circulating tumor DNA and pseudoprogression in patients with metastatic melanoma treated with anti-progressed cell death 1 antibodies -- Chapter 7: Longitudinal monitoring of ctDNA in patients with melanoma and brain metastases treated with immune checkpoint inhibitors -- Chapter 8: Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy -- Chapter 9: Conclusion and Future Directions -- References -- Supplementary material -- AppendixAwarding Institution
Macquarie UniversityDegree Type
Thesis PhDDepartment, Centre or School
Department of Biomedical SciencesYear of Award
2020Principal Supervisor
Helen RizosAdditional Supervisor 1
Matteo S. CarlinoAdditional Supervisor 2
Richard F. KeffordRights
Copyright: Jenny H. Lee
Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimerLanguage
EnglishExtent
193 pages