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2024 World Conference on Lung Cancer (WCLC) - ePos ...
EP.14A.04 Microbial Supernatant Library Screening ...
EP.14A.04 Microbial Supernatant Library Screening Suggested that Induction of Ferroptosis is an Effective Therapeutic Strategy Against Mesothelioma
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The study conducted by Yoshitaka Sekido at the Aichi Cancer Center Research Institute in Japan explored potential therapeutic strategies for mesothelioma, given the limited treatment options currently available. The research focused on the induction of ferroptosis, a type of non-apoptotic cell death, as a promising approach for treating mesothelioma. The study involved screening a library of microbial supernatants to identify compounds that could specifically induce cell death in mesothelioma cell lines.<br /><br />Using this screening approach, the study identified Brefeldin A (BFA) as a compound causing cell death in mesothelioma cells but not in immortalized mesothelial cell lines. While BFA's clinical application is limited due to its toxicity, further experiments using the known ferroptosis inducer RSL3 showed ferroptosis in approximately 50% of the mesothelioma cell lines tested, while others exhibited resistance.<br /><br />Gene expression analysis identified several genes related to ferroptosis sensitivity. Notably, LPCAT1 expression was associated with higher susceptibility to ferroptosis. Knockdown experiments demonstrated that reducing LPCAT1 levels could restore cell viability in sensitive cell lines, indicating its potential role in ferroptosis susceptibility.<br /><br />The study concluded that while a portion of mesothelioma cases are responsive to ferroptosis induction, further investigation into the mechanisms, particularly concerning the role of LPCAT1 and contrasting findings regarding its expression and ferroptosis resistance, is necessary. This research paves the way for developing ferroptosis-based therapeutic strategies, which could offer new hope for treating mesothelioma.<br /><br />The work was supported by various grants, including those from the Japan Society for the Promotion of Science and the Princess Takamatsu Cancer Research Fund.
Asset Subtitle
Yoshitaka Sekido
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Speaker
Yoshitaka Sekido
Topic
Mesothelioma, Thymoma, and Other Thoracic Tumors
Keywords
mesothelioma
ferroptosis
Yoshitaka Sekido
Aichi Cancer Center
Brefeldin A
RSL3
LPCAT1
therapeutic strategies
gene expression
cancer research
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