AUTHOR=Luan Yi , Xian Desheng , Zhao Changwen , Qing Xin , He Hanlin , Zheng Kaixuan , Song Wenjun , Jiang Taijiao , Wang Wenjian , Duan Chaohui 

TITLE=Therapeutic targets for lung cancer: genome-wide Mendelian randomization and colocalization analyses

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1441233

DOI=10.3389/fphar.2024.1441233

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>Lung cancer, categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains a significant global health challenge. The development of drug resistance and the heterogeneity of the disease necessitate the identification of novel therapeutic targets to improve patient outcomes.</p></sec><sec><title>Methods</title><p>We conducted a genome-wide Mendelian randomization (MR) and colocalization analysis using a comprehensive dataset of 4,302 druggable genes and cis-expressed quantitative trait loci (cis-eQTLs) from 31,884 blood samples. The study integrated genomic analysis with eQTL data to identify key genes associated with lung cancer risk.</p></sec><sec><title>Results</title><p>The analysis revealed five actionable therapeutic targets for NSCLC, including LTB4R, LTBP4, MPI, PSMA4, and TCN2. Notably, PSMA4 demonstrated a strong association with both NSCLC and SCLC risks, with odds ratios of 3.168 and 3.183, respectively. Colocalization analysis indicated a shared genetic etiology between these gene expressions and lung cancer risk.</p></sec><sec><title>Conclusion</title><p>Our findings contribute to precision medicine by identifying druggable targets that may be exploited for subtype-specific lung cancer therapies.</p></sec>