2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - ePosters-EP01.06: The Genomic and Transcriptomic Landscape of Recurrent Small Cell Lung Cancer – Pathway Insights and Stratification for Precision Oncology

EP01.06: The Genomic and Transcriptomic Landscape of Recurrent Small Cell Lung Cancer – Pathway Insights and Stratification for Precision Oncology

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The study titled "The Genomic and Transcriptomic Landscape of Recurrent Small Cell Lung Cancer: Pathway Insights and Stratification for Precision Oncology" explores the molecular features of post-treatment small cell lung cancer (SCLC) to better understand mechanisms of treatment resistance and identify potential therapeutic targets. The analysis involved whole-genome sequencing and RNA sequencing of tumors from 21 SCLC patients who had undergone treatment, focusing on the genomic and transcriptomic characteristics associated with resistance to platinum-based chemotherapy.<br /><br />SCLC is known for its aggressive nature, rapid progression, and high mutation rates, particularly involving TP53 and RB1 genes. The study finds significant chromosomal alterations, notably frequent chromosomal gains and losses, with indications of whole-genome doubling in over half of the tumors. These genomic features were analyzed in relation to sex, smoking history, and response to platinum therapy. Notably, all tumors from platinum-sensitive patients showed gains in chromosome 9p, while those from resistant patients did not, highlighting potential genetic markers for treatment response.<br /><br />Transcriptomic analysis categorized tumors into subtypes based on known neuroendocrine markers, revealing that many tumors do not belong to distinct subtypes but rather exist on a continuum, potentially contributing to chemoresistance. The study also identified specific gene mutations, such as in mucin genes, that may influence tumor behavior and therapy resistance.<br /><br />The research highlights distinct expression patterns related to essential signaling pathways, indicating varied vulnerabilities that might be exploited for targeted therapy. The distinction between expression groups based on neuroendocrine and mechanical responsiveness suggests potential avenues for stratification in treatment planning. Despite the small sample size, these findings serve as a foundation for further studies aiming to refine SCLC treatment approaches through a better understanding of its biological variability and resistance mechanisms.

Asset Subtitle

Konstantinos Leventakos

Keywords

Small Cell Lung Cancer

Genomic Landscape

Transcriptomic Analysis

Treatment Resistance

Platinum-based Chemotherapy

Chromosomal Alterations

Neuroendocrine Markers

Gene Mutations

Signaling Pathways

Precision Oncology