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(Slides)

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The document discusses a study that compares the cell cycle responses to two drugs, alectinib and SHP099, in two different variants of ALK non-small cell lung cancer (NSCLC) cell lines. The aim of the study is to determine if there is a synergistic response when the two drugs are combined. <br /><br />The study finds that the combination of alectinib and SHP099 has a synergistic effect at low concentrations in both cell lines. However, the biochemical responses differ between the two cell lines, particularly in the G2/M phase of the cell cycle. In one cell line, there is a decrease in cyclin B1 levels with alectinib alone compared to the combination, while in the other cell line, this effect is not observed. This could be explained by the difference in the number of WD40 repeats in the EML4 domain between the two cell line variants, as these repeats are involved in the organization of mitotic spindles and cell cycle progression.<br /><br />The study also mentions the potential for co-targeting secondary oncogenic drivers, such as SHP2, which is downstream of ALK. By combining ALK and SHP2 inhibitors, it may be possible to restrict the toxicity to cancer cells by reducing the required drug doses.<br /><br />In conclusion, this study demonstrates that there are differing cell cycle responses to alectinib and SHP099 in different variants of ALK NSCLC cell lines. The combination of these drugs shows a synergistic effect, but the specific biochemical responses vary between the cell lines. Further research is needed to investigate apoptotic responses and develop in vitro models to better understand the potential of this combination therapy.

Asset Subtitle

Madeleine Berry

Meta Tag

Speaker Madeleine Berry

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

cell cycle responses

drugs

alectinib

SHP099

ALK non-small cell lung cancer

synergistic response

biochemical responses

G2/M phase

cyclin B1 levels

WD40 repeats