2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.21: MYC-Driven Histological Transformation Contributes to RB1-Proficient Small Cell Lung Cancer

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This study explores the phenomenon of MYC-driven histological transformation in small cell lung cancer (SCLC), particularly focusing on cases that retain the RB1 gene, which is typically lost in these cancers. SCLC is known for its aggressiveness and usual loss of both RB1 and TP53 genes. However, approximately 6-14% of SCLCs retain RB1, presenting a combined histological phenotype with features of both SCLC and non-small cell lung cancer (NSCLC), including associated mutations like KEAP1, FGFR1, and EGFR.<br /><br />The study utilized a genetically engineered mouse model (GEMM) and human lung adenocarcinoma (LUAD) cell lines to illustrate that MYC overexpression can drive the transformation from LUAD to SCLC independently of RB1 loss. This contradicts traditional understanding, where RB1 loss has been considered essential for such transformations. It was observed that RB1-proficient SCLCs could still arise through MYC-driven mechanisms, with SOX2 activation playing a crucial role.<br /><br />The research team developed a novel KPM GEMM model illustrating this MYC-driven transformation process. Their findings suggest a subset of SCLCs can emerge due to distinct pathways, notably MYC overexpression, without the common RB1 deficiency. The implications are significant as they expand the understanding of SCLC origins and suggest potential new therapeutic targets, specifically targeting MYC and SOX2 pathways.<br /><br />The study was supported by various foundations, including the National Natural Science Foundation of China, and the researchers included collaborations from multiple esteemed institutions. Acknowledgments were given to contributors and supporting organizations, emphasizing the collaborative efforts in advancing lung cancer research.

Asset Subtitle

Deshui Jia

Keywords

MYC-driven transformation

small cell lung cancer

SCLC

RB1 gene

histological phenotype

genetically engineered mouse model

LUAD cell lines

SOX2 activation

therapeutic targets

lung cancer research