WCLC 2025 - Posters & ePosters-P3.13.20 Integrative Spatial Analysis Reveals Ferroptosis Heterogeneity and Novel Therapeutic Vulnerabilities in Small Cell Lung Cancer

P3.13.20 Integrative Spatial Analysis Reveals Ferroptosis Heterogeneity and Novel Therapeutic Vulnerabilities in Small Cell Lung Cancer

Back to course

Pdf Summary

This study presents an integrative spatial multi-omics analysis of small cell lung cancer (SCLC) to uncover ferroptosis heterogeneity and identify novel therapeutic vulnerabilities. Utilizing a clinical cohort of 100 limited-stage SCLC patients from the Fudan University SCLC (FU-SCLC) cohort, the research applied a combination of genomic, transcriptomic, metabolomic, lipidomic, spatial single-cell transcriptomic (CosMx), and proteomic (CODEX) sequencing to achieve a robust molecular classification of SCLC.<br /><br />Three distinct SCLC subtypes were identified: proliferative, immunogenic, and metabolic reprogramming (MR) subtypes, each associated with unique clinical outcomes and spatial molecular characteristics. The MR subtype demonstrated notably increased glycolytic and tricarboxylic acid cycle activity, signaling altered metabolic states. Intriguingly, this subtype exhibited aberrant activation of the non-canonical ferroptosis defense axis DHODH-COQH2, suggesting a novel mechanism by which these cancer cells evade ferroptotic cell death.<br /><br />These findings highlight significant ferroptosis heterogeneity across SCLC tumors, emphasizing the critical need for personalized treatment approaches tailored to individual patient molecular landscapes. The characterization of distinct metabolic and immune profiles within subtypes offers potential new therapeutic targets, especially by exploiting vulnerabilities such as disrupted ferroptosis pathways.<br /><br />Overall, this work provides pivotal insights into the biology of SCLC and establishes a valuable resource for future molecular investigations. By integrating spatial and multi-omics data, the study reveals diverse SCLC phenotypes with distinct therapeutic susceptibilities, paving the way for precision medicine strategies aimed at improving outcomes in this challenging cancer type.

Asset Subtitle

Chaoqiang Deng

Meta Tag

Speaker Chaoqiang Deng

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small cell lung cancer

ferroptosis heterogeneity

spatial multi-omics

SCLC subtypes

metabolic reprogramming

DHODH-COQH2 axis

glycolysis

tricarboxylic acid cycle

personalized treatment

precision medicine