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Marshall, Erin A.

University of British Columbia

Lung cancer is the leading cause of cancer related death worldwide. This poor survival rate can be attributed in part to late disease detection, in addition to a lack of adequate biomarkers to predict disease onset. In addition to known genetic lung cancer drivers, we know that the tumour microenvironment, in particular the involvement of the immune system, plays a major role in lung cancer progression, therapy, and prognosis. Work from recent years has highlighted the importance of the tumour microenvironment, particularly the tumour-resident microbiome, in lung cancer outcome. There is a need for the development of new biomarkers to identify lung tumours early in pathogenesis as well as the potential for new therapeutic targets that harness the power of the tumour microenvironment for improved patient outcomes. The goal of this work was to assess how the tumour microenvironment, including the tumour-resident microbiome, may play a role in cancer initiation and progression. The overarching hypothesis of this work is that lung tumour initiation and progression is influenced by microbes in the tumour microenvironment, in addition to genetic alterations in the tumour cells. In this thesis, we examine how the distinct COPD microenvironment may contribute to the development of lung cancer. Further, within patients at high-risk of lung cancer, we find that the airway microbiome is able to predict which individuals will be diagnosed with lung cancer. We then find that in the tumour itself, the tumour niche selects for bacteria that produce L-methionine, an essential amino acid that is growth-limiting in tumour models. We conclude by highlighting how emerging technologies can be used to advance what is known about these microbe-host interactions. Together, these findings emphasize the importance of the microbiome in the solid tumour niche, and raise the importance of considering the characteristics of the unique tumour niche in lung cancer therapy and for disease risk stratification in high-risk patients.

Text

2022-06-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/79144

Interdisciplinary Oncology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/