2023 World Conference on Lung Cancer (Posters)-EP02.01. Differing Cell Cycle Responses for Alectinib and SHP099 in Variant 1 and Variant 3 ALK+ Non-Small Cell Lung Cancer Cell Lines

EP02.01. Differing Cell Cycle Responses for Alectinib and SHP099 in Variant 1 and Variant 3 ALK+ Non-Small Cell Lung Cancer Cell Lines - PDF(Abstract)

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This document is a summary of a presentation at the WCLC 2023 conference. The presentation titled "Differing Cell Cycle Responses for Alectinib and SHP099 in Variant 1 and Variant 3 ALK Non-Small Cell Lung Cancer Cell Lines" discusses the differences in cell cycle responses to two drugs, Alectinib and SHP099, in two different variants of ALK non-small cell lung cancer (NSCLC) cell lines.<br /><br />Lung cancer is a leading cause of cancer death worldwide, and NSCLC accounts for 85% of cases. ALK NSCLC is a specific type of NSCLC driven by the anaplastic lymphoma kinase (ALK) molecular target. Alectinib is an ALK inhibitor used for the treatment of ALK NSCLC, but resistance can develop over time. This study explores the possibility of combining Alectinib with an SHP2 inhibitor, SHP099, to improve drug efficacy.<br /><br />The study uses two different ALK NSCLC cell lines, H3122 (Variant 1) and H2228 (Variant 3), to compare the cell cycle responses to the combination of Alectinib and SHP099. The researchers evaluate cell viability using the sulforhodamine B assay and assess changes in the cell cycle using flow cytometry and Western blotting.<br /><br />The results show that there is a synergistic decrease in cell viability with the combination of Alectinib and SHP099 in both cell lines at low concentrations. However, there are differences in the cell cycle responses between the two variants. The H3122 cells exhibit a G1-phase cell cycle arrest, while the H2228 cells do not show significant changes in the cell cycle phases.<br /><br />The differences in cell cycle response can be explained by the structural differences in the EML4 domain of each variant. Variant 3 has fewer WD40 repeats, which are involved in mitotic spindle organization and progression. Future experiments will investigate apoptotic responses and the development of an in vitro spheroid model.<br /><br />In summary, this study provides insights into the cell cycle responses of two different ALK NSCLC variants to the combination of Alectinib and SHP099. The findings suggest potential differences in drug efficacy and highlight the importance of understanding the molecular characteristics of different cancer variants.

Asset Subtitle

Madeleine Berry

Meta Tag

Speaker Madeleine Berry

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

WCLC 2023 conference

cell cycle responses

Alectinib

SHP099

ALK non-small cell lung cancer

NSCLC

cell lines

drug efficacy

cell viability

cell cycle phases