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Mechanisms of Early-Stage Mutant EGFR-Driven Lung Cancer: The Role of Kynurenine

Lung cancer initiation and progression driven by epidermal growth factor receptor (EGFR) mutation has been extensively studied in the past decade. EGFR mutation is a significant driver of tumorigenesis and inflammation. This receptor is directly related to many downstream pathways that influence cancer metabolism and the ability of tumor cells to adapt to changes in the tumor microenvironment. Our study finds that cancer metabolism plays a large role in the progression of tumorigenesis in early-stage lung cancer. Kynurenine (KYN), a metabolite from the tryptophan pathway, was found to be highly upregulated in early-stage, EGFR-mutation driven lung cancer by metabolomic analysis. The connection between EGFR mutation and the upregulation of kynurenine remains largely unknown. Our data also shows that a significant pathway related to precancer initiation is systemic lupus erythematosus (SLE). We hypothesize that kynurenine may have a dual role in early tumorigenesis. We propose that high levels of kynurenine may be a part of metabolic reprogramming caused by genetic regulation of indoleamine 2,3-dioxygenase 1/2 (IDO1/2). Additionally, kynurenine may be used as a signaling molecule in the tumor microenvironment to allow the early tumor cells to evade immune detection. Our study has implications for the early treatment of lung cancer and provides insight into a potential clinical target in the tryptophan pathway.

Identiferoai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2771
Date15 August 2023
CreatorsRodriguez-Fuguet, Alice
PublisherSTARS
Source SetsUniversity of Central Florida
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceElectronic Theses and Dissertations, 2020-

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