Author ORCID Identifier

https://orcid.org/0000-0002-1161-7976

Date of Graduation

6-2018

Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Xiangwei Wu

Committee Member

Anil K. Sood

Committee Member

Samir M. Hanash

Committee Member

Jichao Chen

Committee Member

Paul Chiao

Abstract

Lung cancer is the most common cause of cancer related death in the United States and worldwide. It has been shown that 30%-55% of patients with early stages of non-small cell lung cancer (NSCLC) developed and died of recurrence after curative resection, suggesting that tumor cell dissemination occurred early in those patients before surgery. However, molecular evidence, underline mechanisms and risk factors for the NSCLC relapse remain largely unknown. Addressing these questions will be critical for the development of strategies to stratify the risk of recurrence and approaches to reduce these risks. My thesis focused on dissecting the molecular basis of early tumor cell dissemination (ETCD) using mouse models of NSCLC. First, we established and characterized a new mouse model of NSCLC using lung specific activation of an epidermal growth factor receptor (EGFR) mutant form in combination with loss of p53. Using this model and an oncogene Kras–driven lung cancer model, we identified that the combination of inflammation and stress is a major contributor to induce ETCD. A small number of the early disseminated tumor cells (

Keywords

NSCLC, CTC, early cancer dissemination, inflammation, stress

Available for download on Tuesday, June 04, 2019

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