2024 World Conference on Lung Cancer (WCLC) - Posters-P2.14A.09 Adaptive Reprogramming of Arginine Biosynthesis is an Attractive Target for Modulating the Response to WEE1 Inhibition in Pleural Mesothelioma

P2.14A.09 Adaptive Reprogramming of Arginine Biosynthesis is an Attractive Target for Modulating the Response to WEE1 Inhibition in Pleural Mesothelioma

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The document discusses research focused on pleural mesothelioma, highlighting the adaptive reprogramming of arginine biosynthesis as a potential target for improving the response to WEE1 inhibition, a promising therapeutic approach for this cancer. The study's alignment involved a genome-wide CRISPR-mediated knockout screen to identify genes influencing mesothelioma cells' resistance or sensitivity to WEE1 inhibition. Through this screening process, the researchers identified potential genetic vulnerabilities and key pathways linked to drug resistance.<br /><br />Their investigation revealed that arginine biosynthesis is a significant molecular alteration in cell populations resistant to WEE1 inhibition. This was discovered through unbiased transcriptomics and metabolomics profiling, which provided insights into the distinct genetic and metabolic characteristics of parental versus resistant cell populations. The integrated pathway analysis using enrichment methods like Mummichog highlighted that alterations in arginine biosynthesis could be exploited to modulate the efficacy of WEE1 inhibitors.<br /><br />Arginine biosynthesis, being ranked highly among the molecular pathways altered in resistant cells, suggests its potential as a therapeutic target for overcoming resistance in mesothelioma treatment. By manipulating this pathway, the response to WEE1 inhibitors could be improved, offering new potential treatments for patients suffering from pleural mesothelioma.<br /><br />This study underscores the importance of understanding metabolic reprogramming in cancer cells, as it provides critical insights into overcoming drug resistance, ultimately aiming to enhance current therapeutic strategies against this aggressive form of cancer.

Asset Subtitle

Duo Xu

Meta Tag

Speaker Duo Xu

Topic Mesothelioma, Thymoma & Other Thoracic Tumors

Keywords

pleural mesothelioma

arginine biosynthesis

WEE1 inhibition

CRISPR knockout screen

drug resistance

genetic vulnerabilities

transcriptomics

metabolomics

pathway analysis

cancer treatment