2023 World Conference on Lung Cancer (Posters)-P1.02. Identifying Biomarkers of Response to Ensartinib, Lorlatinib, and Alectinib in an ALK+ Non-Small Cell Lung Cancer Preclinical Model (ResCu)

P1.02. Identifying Biomarkers of Response to Ensartinib, Lorlatinib, and Alectinib in an ALK+ Non-Small Cell Lung Cancer Preclinical Model (ResCu) - PDF(Abstract)

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This study aimed to identify biomarkers that can predict the response to ALK inhibitors lorlatinib, alectinib, and ensartinib in ALK non-small cell lung cancer. The researchers used a long-term cell culture model called ResCu to develop resistant cell populations. They used two ALK-dependent lung adenocarcinoma cell lines and evolved resistance to the inhibitors over time. The researchers then performed single-cell RNA sequencing and bulk RNA and whole exome sequencing to identify biomarkers of resistance. They also collected clinical samples from patients before treatment with ALK inhibitors and performed spatial transcriptomics. <br /><br />The results showed that the ResCu system successfully developed ensartinib, alectinib, and lorlatinib resistant cell populations. The genetic background of the cells had a significant impact on which inhibitor showed the most durable response. The researchers identified 124 genomic and transcriptomic alterations associated with resistance to one or more ALK inhibitors. Only 5 of these biomarkers were common to all three inhibitors, and 10 were indicative of resistance to two inhibitors. The spatial transcriptomics analysis of patient samples confirmed the presence of these biomarkers before ALK inhibitor exposure. <br /><br />In conclusion, this study demonstrated the use of the ResCu system to develop resistant cell populations and identify biomarkers of response to ALK inhibitors. The genetic background of the cells played a role in the response to different inhibitors. The identified biomarkers provide potential targets for future research and may aid in personalized treatment selection for ALK non-small cell lung cancer patients.

Asset Subtitle

Christopher Bulow

Meta Tag

Speaker Christopher Bulow

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

biomarkers

ALK inhibitors

lorlatinib

alectinib

ensartinib

ALK non-small cell lung cancer

ResCu

genomic alterations

transcriptomic alterations

spatial transcriptomics