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