2022 World Conference on Lung Cancer (ePosters)-EP14.02-004. Barasertib Inhibits the Growth of SCLC Cell Lines and Transformed SCLC Patient Derived Model In Vitro and In Viv

EP14.02-004. Barasertib Inhibits the Growth of SCLC Cell Lines and Transformed SCLC Patient Derived Model In Vitro and In Viv

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This study investigated the therapeutic potential of targeting aurora kinase with barasertib in small cell lung cancer (SCLC) subtypes. Approximately 5-10% of non-small cell lung cancers (NSCLCs) with EGFR mutations develop acquired resistance and transform into SCLC. Four SCLC subtypes were defined based on differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factors. Barasertib, an Aurora B inhibitor, was tested for its anti-proliferative activity in different SCLC cell lines. It specifically inhibited cell growth in the POU2F3-positive SCLC subtype as well as in patient-derived cells (PDC). The inhibition of Aurora B by barasertib was confirmed by reduced phosphorylation of Histone H3 Serine 10, a specific substrate for Aurora B. In a PDX (patient-derived xenograft) mouse model, barasertib demonstrated profound anti-tumor efficacy without significant toxicity. These findings suggest that targeting aurora kinase with barasertib may be a promising therapeutic approach for SCLC-P subtype cells and could be further explored in clinical settings. The study provides insights into the molecular characteristics and vulnerabilities of different SCLC subtypes and highlights the potential of barasertib as a targeted therapy for SCLC.

Asset Subtitle

Jin Soo Kim

Meta Tag

Speaker Jin Soo Kim

Topic Small Cell Lung Cancer and Neuro-endocrine Tumours - Preclinical/Translational

Keywords

aurora kinase

barasertib

small cell lung cancer

SCLC subtypes

transcription factors

cell growth inhibition

Aurora B inhibitor

anti-proliferative activity

patient-derived cells

targeted therapy