2022 World Conference on Lung Cancer (ePosters)-EP14.02-006. Subtype-specific Hypersensitivity to Oxidative Phosphorylation Inhibition in Small Cell Lung Cancer

EP14.02-006. Subtype-specific Hypersensitivity to Oxidative Phosphorylation Inhibition in Small Cell Lung Cancer

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Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis. In this study, researchers investigated the role of oxidative phosphorylation (OXPHOS) in different molecular subtypes of SCLC and its potential as a target for therapy.<br /><br />The study found that the SCLC-A molecular subtype had significantly upregulated proteins involved in the electron transport chain of OXPHOS compared to other subtypes. Proteomic analysis confirmed increased OXPHOS in ASCL1-expressing SCLC cell lines. These findings suggest that targeting the upregulated OXPHOS in the SCLC-A subtype could be a potential therapeutic approach.<br /><br />The study further explored the sensitivity of SCLC-A cells to specific inhibitors of OXPHOS, including perhexiline, metformin, and IACS-010759. The results showed that these inhibitors were effective in reducing cell viability in SCLC-A cells, indicating the hypersensitivity of these cells to OXPHOS inhibition.<br /><br />Additionally, the study analyzed the gene expression profiles of SCLC tumors and found that the SCLC-A subtype exhibited enrichment of the OXPHOS process compared to other subtypes. This further supports the potential of targeting OXPHOS in the treatment of SCLC-A patients.<br /><br />Overall, this study highlights the subtype-specific hypersensitivity of SCLC-A cells to OXPHOS inhibition, suggesting that targeting OXPHOS could be a promising therapeutic strategy for a subset of SCLC patients. Further research is needed to validate these findings and explore the clinical implications of targeting OXPHOS in SCLC-A patients.

Asset Subtitle

Kristiina Boettiger

Meta Tag

Speaker Kristiina Boettiger

Topic Small Cell Lung Cancer and Neuro-endocrine Tumours - Preclinical/Translational

Keywords

Small cell lung cancer

SCLC

aggressive cancer

prognosis

oxidative phosphorylation

molecular subtypes

targeted therapy

electron transport chain

proteomic analysis

therapeutic approach