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A multidimensional approach to understanding lung tumour aggressiveness

University of British Columbia

Lung cancer is a deadly disease with a 5-year survival of 18%. Patients with localized disease have improved outcomes, since they are eligible for surgery with curative intent. However, the majority of patients present with metastatic disease, where treatment options are limited. Genetic profiling of lung tumours has lead to the identification of driver mutations and the subsequent development of targeted therapies for some of these mutated genes, which has resulted in improved outcomes for late stage patients. Unfortunately, only subsets of patients harbour these mutations, and patients frequently acquire drug resistance. Novel therapeutics are desperately needed for patients with late stage disease in order to improve patient outcome. To achieve this goal, we require a deeper understanding of the biology that drives aggressive lung tumour biology. In this thesis, we employ two unique approaches to discover genes associated with lung tumour aggressiveness. Firstly, we move beyond the protein-coding landscape and characterize deregulation of small non-coding RNAs in metastatic lung cancer. We further assess the ability of small non-coding RNA expression patterns to classify patients into different outcome groupings. Secondly, we employ an integrative multi-omics approach in order to identify novel oncogenes that have been overlooked by conventional studies within a single dimension (e.g. mutation). Collectively, this work adds to our understanding of aggressive tumour biology. Further characterization of the aggressiveness-associated small non-coding RNAs identified here may inform on novel therapeutic avenues or gene signatures. Importantly, our discovery of a novel lung cancer oncogene may lead to a new therapy for lung cancer.

Text

2018-06-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/62058

Interdisciplinary Oncology

University of British Columbia

UBCV

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