WCLC 2025 - Posters & ePosters-P2.06.79 Deciphering Genomic and Transcriptomic Heterogeneity in Circulating Tumor Cells at Diagnosis in Small Cell Lung Cancer: CTC-CPC Study

P2.06.79 Deciphering Genomic and Transcriptomic Heterogeneity in Circulating Tumor Cells at Diagnosis in Small Cell Lung Cancer: CTC-CPC Study

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The CTC-CPC study investigates circulating tumor cells (CTCs) in Small Cell Lung Cancer (SCLC) to understand tumor heterogeneity at diagnosis. SCLC, an aggressive cancer with poor prognosis, has recently been classified into four molecular subtypes defined by key transcription factors: ASCL1, NEUROD1, POU2F3, and a triple-negative group. Traditional tumor biopsies often fail due to tumor necrosis, making CTCs a crucial non-invasive resource.<br /><br />The study involved 22 SCLC patients, mostly male, with a median age of 62.5 years, predominantly diagnosed at disseminated stages. First-line treatments included platinum doublets, with or without immunotherapy or radiotherapy. CTC counts at diagnosis varied widely among patients.<br /><br />Genomic analysis of CTCs revealed a high mutational burden and significant ploidy variability. Copy number alteration profiling identified two distinct CTC clusters: one with predominant gene amplifications and another with dominant deletions. Pathway analyses showed differences between CTCs and primary tumor tissues, highlighting unique biological alterations present in circulating cells.<br /><br />Transcriptomic profiling using digital droplet PCR in established SCLC cell lines confirmed the expression patterns of subtype-defining transcription factors, validating the method. Further, subtype-specific expression was successfully detected in spiked blood samples, demonstrating feasibility for non-invasive molecular subtyping.<br /><br />Overall, the study underscores the value of CTCs as a liquid biopsy tool to capture intratumoral heterogeneity, enabling molecular subtyping in SCLC, which could guide tailored therapeutic strategies. This approach may help overcome limitations of traditional biopsies and inform personalized patient management in this challenging cancer type. The study received support from several research foundations and benefited from bioinformatics and technical expertise across collaborating institutions.

Asset Subtitle

Charles Ricordel

Meta Tag

Speaker Charles Ricordel

Topic Pathology and Biomarkers

Keywords

Small Cell Lung Cancer

Circulating Tumor Cells

Tumor Heterogeneity

Molecular Subtypes

ASCL1

NEUROD1

POU2F3

Liquid Biopsy

Copy Number Alterations

Transcriptomic Profiling