2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.170 (Poster) The Role of Fat Mass and Obesity-Associated (FTO) Gene in Non-small Cell Lung Cancer Tumorigenicity and EGFR Tyrosine Kinase Inhibitor Resistance

PP01.170 (Poster) The Role of Fat Mass and Obesity-Associated (FTO) Gene in Non-small Cell Lung Cancer Tumorigenicity and EGFR Tyrosine Kinase Inhibitor Resistance

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Lung cancer is the leading cause of cancer-related deaths and the third most common type of cancer in the United States. Non-small cell lung cancer (NSCLC) is the most common type, accounting for 80% of cases. The survival rate for NSCLC is low, with only 25.4% of patients surviving for 5 years. Early-stage diagnosis has a higher survival rate compared to advanced-stage diagnosis. Adenocarcinoma is the most common subtype of NSCLC.<br /><br />Epidermal Growth Factor Receptor (EGFR) mutations are the most common oncogenic drivers in NSCLC, with overexpression in 40% of cases. Erlotinib and osimertinib are effective in treating NSCLC by binding to the tyrosine kinase domain of EGFR. However, resistance to these treatments develops after 9-12 months.<br /><br />Recent research has identified the fat mass and obesity-associated (FTO) protein as a factor contributing to therapy resistance and tumor growth in various cancer types, including lung cancer. FTO is responsible for demethylating nuclear m6A of mRNA. However, the role of FTO in tumorigenesis is still controversial.<br /><br />The study aimed to investigate the role of FTO in NSCLC tumorigenicity and resistance to EGFR tyrosine kinase inhibitors (TKIs). The study found that FTO expression was significantly upregulated in late-stage NSCLC tumor tissues and EGFR TKI resistant NSCLC cell lines. Inhibition or knockdown of FTO reduced cell survival and migratory capacity in the resistant cells.<br /><br />The findings suggest that FTO plays an important role in tumor growth and EGFR TKI resistance in NSCLC. FTO may promote resistance by enhancing cell proliferation and expansion. Combining FTO inhibition with EGFR TKIs may overcome resistance and improve treatment outcomes.<br /><br />In conclusion, FTO expression is elevated in late-stage NSCLC tumor tissues and EGFR TKI resistant NSCLC cell lines. FTO plays a role in promoting tumor growth and resistance to EGFR TKIs. Further research is needed to understand the exact mechanisms involved and to explore FTO as a potential prognostic marker and therapeutic target in NSCLC.

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Rong Chloe Qui

Keywords

Lung cancer

NSCLC

adenocarcinoma

EGFR mutations

tyrosine kinase inhibitors

therapy resistance

tumor growth

FTO protein

tumorigenicity

EGFR TKIs