2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.17: Reconstructing small cell lung cancer evolution using deep whole genome sequencing of circulating tumor DNA

PP01.17: Reconstructing small cell lung cancer evolution using deep whole genome sequencing of circulating tumor DNA

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This study, conducted by researchers including Benjamin B. Morris and colleagues from The University of Texas MD Anderson Cancer Center, investigates the evolution of small cell lung cancer (SCLC) using deep whole genome sequencing of circulating tumor DNA (ctDNA). SCLC is a particularly lethal cancer, often showing significant evolution following therapy, and poses challenges due to the lack of durable response to frontline therapies, such as the etoposide-cisplatin/carboplatin with anti-inflammatory immunotherapy (EPIO). Since most patients present with extensive-stage disease and do not undergo surgery, traditional collection of tumor samples is not feasible.<br /><br />The researchers employed a minimally invasive technique by leveraging ctDNA obtained from patients’ blood samples, which offers a viable alternative to traditional biopsies. This approach can capture the genetic landscape of SCLC by performing whole genome sequencing on ctDNA and germline DNA, enabling the identification of somatic mutations, structural variants, and subclonal copy number alterations that occur in response to treatment.<br /><br />The results indicate that deep WGS of ctDNA effectively captures the genetic changes in SCLC and can detect significant tumor evolution following frontline EPIO therapy. Some SCLCs show substantial genomic evolution, while others suggest non-genomic factors might drive therapy resistance. The study also highlights cases of ongoing genomic evolution even during rechallenges with therapy, underlining the complexity of SCLC resistance mechanisms.<br /><br />Overall, the study underscores the feasibility and utility of using ctDNA for tracking tumor evolution over time, providing insights into the genomic mechanisms of therapy resistance in SCLC. These findings could potentially guide the development of new therapeutic strategies tailored to address the evolving nature of this aggressive cancer type.

Asset Subtitle

Benjamin Morris

Keywords

small cell lung cancer

circulating tumor DNA

deep whole genome sequencing

therapy resistance

genomic evolution

minimally invasive technique

tumor evolution

somatic mutations

structural variants

subclonal copy number alterations