2023 World Conference on Lung Cancer (Posters)-EP10.01. DDR1 Mediated Glycolysis Regulates the Synergistic Effect of Anlotinib and Docetaxel in Lung Cancer

EP10.01. DDR1 Mediated Glycolysis Regulates the Synergistic Effect of Anlotinib and Docetaxel in Lung Cancer - PDF(Slides)

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In this study, researchers from Hangzhou First People's Hospital in China investigated the synergistic effect of the combination of anlotinib and docetaxel in treating advanced non-small cell lung cancer (NSCLC). They explored the potential mechanism behind their collaborative action and focused on discoidin domain receptor (DDR1) and glycolysis.<br /><br />The researchers conducted various experiments using A549 lung cancer cells, including cell viability assays, clone formation experiments, flow cytometry analysis for apoptosis, and molecular assays to detect DDR1 expression. They also constructed xenograft models and analyzed the protein profiles in the tumors. Additionally, data from The Cancer Genome Atlas (TCGA) was used to evaluate the effect of DDR1 on NSCLC prognosis.<br /><br />The results showed that DDR1 mRNA expression was higher in tumor tissue and was associated with poor prognosis in NSCLC. Docetaxel treatment induced DDR1 phosphorylation, and blocking or silencing DDR1 enhanced the activity of docetaxel. Anlotinib, on the other hand, inhibited DDR1 phosphorylation and increased the sensitivity of docetaxel both in vitro and in vivo.<br /><br />Proteomic analysis revealed that anlotinib disrupted glycolytic metabolism, and cellular experiments showed that it downregulated the expression of GLUT1, a key enzyme of glycolysis. Knockdown of DDR1 also downregulated GLUT1 expression and attenuated the synergistic effect of anlotinib and docetaxel.<br /><br />The researchers concluded that anlotinib suppresses DDR1 phosphorylation, downregulates GLUT1 expression, and inhibits glycolysis. This promotes the antitumor activity of docetaxel in NSCLC. They believe that their study not only uncovered new mechanisms of anlotinib but also provided strong support for combining anlotinib and docetaxel in clinical practice for the treatment of NSCLC.

Asset Subtitle

Xueqin Chen

Meta Tag

Speaker Xueqin Chen

Topic Metastatic NSCLC: Cytotoxic Therapy

Keywords

anlotinib

docetaxel

NSCLC

synergistic effect

DDR1

glycolysis

prognosis

phosphorylation

GLUT1 expression

antitumor activity