2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.39 Elucidating the Role of ISL1 as a Predictive Biomarker for Lurbinectedin Response in Small Cell Lung Cancer

PP01.39 Elucidating the Role of ISL1 as a Predictive Biomarker for Lurbinectedin Response in Small Cell Lung Cancer

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The study investigates the role of the transcription factor ISL1 as a predictive biomarker for the response to lurbinectedin in Small Cell Lung Cancer (SCLC). SCLC is a highly aggressive cancer with a high relapse rate, prompting the need for effective treatments. Lurbinectedin, an alkylating agent approved in 2020, binds DNA to inhibit RNA polymerase II and modify the tumor microenvironment, but its effectiveness can vary. Despite SLFN11 being proposed as a biomarker, it has not consistently predicted response to lurbinectedin. Through proteomics and experiments with SCLC cell lines, ISL1 emerged as a significant indicator for sensitivity to lurbinectedin.<br /><br />The study utilized several methodologies, including cell viability assays, Western blotting, quantitative PCR, and RNA sequencing, to assess the association between ISL1 expression levels and lurbinectedin sensitivity. Results indicated that cell lines with high ISL1 expression are more sensitive to lurbinectedin. ISL1 expression decreases following treatment, as demonstrated by reduced RNA and protein levels. Moreover, the reduction of ISL1 via RNA interference led to decreased expression of ASCL1, a gene also linked to lurbinectedin sensitivity.<br /><br />Conclusively, ISL1 appears to be differentially expressed in SCLC cell lines and its expression correlates with increased sensitivity to lurbinectedin, potentially serving as a biomarker for this treatment. Future research directions include studying the interactions between ISL1 and other transcription factors such as SOX5 and assessing changes in ISL1 expression over time. The study is funded by multiple sources, including the State of Florida Bankhead Cancer Research Program and Indiana University Simon Comprehensive Cancer Center.

Asset Subtitle

Olivia Terry

Keywords

ISL1

lurbinectedin

Small Cell Lung Cancer

SCLC

biomarker

transcription factor

proteomics

cell viability assays

RNA sequencing

ASCL1