2023 World Conference on Lung Cancer (Posters)-P1.06. Phenotype Mapping of Patient-Derived Small Cell Lung Cancer Organoids Illuminate Subtype-Specific Therapeutic Vulnerability

P1.06. Phenotype Mapping of Patient-Derived Small Cell Lung Cancer Organoids Illuminate Subtype-Specific Therapeutic Vulnerability - PDF(Abstract)

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Pdf Summary

Small cell lung cancer (SCLC) is a devastating disease with different molecular subtypes. This study aimed to connect these subtypes with therapeutic vulnerability. The researchers established a patient-derived SCLC organoid library consisting of 30 organoid lines. They conducted comprehensive molecular profiling and analysed the cell-intrinsic pathway dependency of the SCLC cells. The library was developed using various clinical samples, and immunohistochemical staining confirmed the preservation of neuroendocrine marker proteins in the organoids. Genetic alterations in TP53 and RB1 genes were observed through whole exome sequencing, and four transcription factor subtypes were confirmed through RNA sequencing. The niche dependency analysis revealed specific dependency of POU2F3 and YAP1-type SCLC. Drug sensitivity assays demonstrated the efficacy of molecular target inhibitors for SCLC in a subtype-specific manner, both in vitro and in vivo. <br /><br />In conclusion, the researchers have established a clinically relevant and tractable research model for the SCLC research community. They propose using organoid-based phenotype mapping to connect SCLC subtypes with therapeutic vulnerability. This research contributes to the understanding and development of treatment for this devastating disease.

Asset Subtitle

Takahiro Fukushima

Meta Tag

Speaker Takahiro Fukushima

Topic Tumor Biology: Preclinical Biology - Tumor Immunity

Keywords

Small cell lung cancer

SCLC

molecular subtypes

therapeutic vulnerability

organoid library

genetic alterations

transcription factor subtypes

RNA sequencing

molecular target inhibitors

treatment development