2022 World Conference on Lung Cancer (ePosters)-EP16.04-002. Combining Patient-Derived Xenografts and Barcoding Technology to Evaluate Response to Targeted Therapies in ALK+NSCLC

EP16.04-002. Combining Patient-Derived Xenografts and Barcoding Technology to Evaluate Response to Targeted Therapies in ALK+NSCLC

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This study explores the use of patient-derived xenografts (PDX) and single-cell barcoding technology to evaluate the response to targeted therapies in anaplastic lymphoma kinase (ALK)-oncogene addicted non-small cell lung cancers (NSCLC). Currently, most patients with ALK-positive NSCLC develop resistance to ALK-specific small molecule inhibitors, and resistance can only be determined at endpoints in clinical settings. Therefore, finding biomarkers and predicting clinical outcomes based on molecular features is important for optimizing ALK-directed therapies.<br /><br />The researchers aimed to characterize and validate targets emerging in ALK-positive lung cancer under ALK-directed therapies and analyze the molecular differences between tumors that respond or are resistant to these therapies in vivo. They created well-characterized patient-derived ALK-positive tumor models and used a lentiviral delivery system for molecular single-cell barcoding. These tumor models were then injected into immunosuppressant mice and treated with ALK-specific small molecule inhibitors to identify potentially actionable driver mutations. In vitro screens were also performed to assess ALK-specific inhibitor sensitivity.<br /><br />The results showed that the barcoding platform used was effective in labeling patient-derived lung cancer cells, and the sequencing strategy confirmed the generation of unique barcodes. The ALK inhibitors Ceritinib and Brigatinib were able to control cell viability in vitro but not abolish it, suggesting adaptive processes. In an in vivo model, Ceritinib treatment only controlled tumor growth, while treatment with Brigatinib enabled tumor growth control. These findings suggest that different ALK inhibitors may have varying efficacy in ALK-positive lung cancer.<br /><br />Overall, this study demonstrates the potential of using PDX models and single-cell barcoding technology to evaluate the response to targeted therapies in ALK-positive NSCLC. Understanding the molecular differences between responder and non-responder tumors can aid in guiding individual treatment decisions for patients with ALK-positive lung cancer.

Asset Subtitle

Anne Petzold

Meta Tag

Speaker Anne Petzold

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

patient-derived xenografts

single-cell barcoding technology

targeted therapies

anaplastic lymphoma kinase

ALK-oncogene addicted non-small cell lung cancers

biomarkers

clinical outcomes

molecular features

ALK-directed therapies

tumor models