2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.01: Multi-site profiling of small cell lung cancer and assessment of tumor heterogeneity through rapid research autopsy

PP01.01: Multi-site profiling of small cell lung cancer and assessment of tumor heterogeneity through rapid research autopsy

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This study investigates the heterogeneity and molecular characteristics of small cell lung cancer (SCLC) by examining multiple tumor samples obtained through a rapid research autopsy (RRA) program. The research aims to uncover mechanisms behind SCLC's cell plasticity and to identify new, broadly applicable therapeutic targets unaffected by tumor heterogeneity.<br /><br />The researchers collected representative tissue samples from 23 patients, totaling 194 tumor specimens and 60 non-tumorous controls, all gathered within four hours post-mortem. Samples included primary tumors and metastatic lesions from various organs such as the lung, liver, brain, and adrenal gland. These samples underwent RNA sequencing, proteomic analysis, and immunohistochemistry to evaluate tumor heterogeneity, cell plasticity, and the expression of molecular subtypes.<br /><br />Results demonstrated moderate to high variability in the expression of known therapeutic targets like ANXA1, CD47, VEGFA, and TGFB1 across metastatic sites. However, they identified 62 consistently expressed proteins in tumors that could serve as potential therapeutic targets. Immunohistochemistry revealed a novel subtype (SCLC-A-inflamed) with high ASCL1 expression and a unique inflamed phenotype. Notably, the dominant molecular subtype varied across metastatic sites in 85% of the patients.<br /><br />The study underscores significant inter-tumoral heterogeneity in SCLC, providing insights into its complex biology. The stable expression of specific proteins across tumors highlights potential new drug targets. These findings could contribute to developing more effective treatments by catering to the aggressive biology of SCLC. Further validation and clinical testing are required to confirm these targets' utility in enhancing therapeutic options for SCLC, a notoriously challenging cancer to treat.

Asset Subtitle

Zsolt Megyesfalvi

Keywords

small cell lung cancer

tumor heterogeneity

molecular characteristics

rapid research autopsy

therapeutic targets

cell plasticity

RNA sequencing

proteomic analysis

immunohistochemistry

SCLC-A-inflamed