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(Abstract)

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In this study presented at the WCLC 2023 conference, the researchers investigated the potential mechanism behind the synergistic effect of the combination of anlotinib and docetaxel in the treatment of non-small cell lung cancer (NSCLC). They focused on the role of discoidin domain receptor (DDR1) and glycolysis in this collaborative action.<br /><br />Previous clinical trials had already shown that the combination of anlotinib, an anti-angiogenic agent, with docetaxel provided improved clinical benefits for advanced NSCLC patients who had failed platinum-based chemotherapy. However, the underlying mechanism of this synergy was unclear.<br /><br />The researchers found that DDR1 was more highly expressed in tumor tissue compared to normal tissue and was associated with poor prognosis in NSCLC. Anlotinib enhanced the antitumor activity of docetaxel in A549 cell lines and xenograft models derived from patients or cells. They also observed that docetaxel induced DDR1 phosphorylation, while anlotinib inhibited this phosphorylation, increasing the sensitivity of docetaxel.<br /><br />Moreover, anlotinib disturbed glycolytic metabolism and downregulated the expression of GLUT1, a key enzyme in glycolysis. Silencing DDR1 or knockdown also enhanced the activity of docetaxel and reduced the synergistic effect of anlotinib and docetaxel. Silencing DDR1 also downregulated GLUT1 expression and attenuated the synergistic effect of the combination therapy in xenograft models.<br /><br />In conclusion, anlotinib suppresses DDR1 phosphorylation, downregulates GLUT1 expression, and inhibits glycolysis, thereby promoting the antitumor activity of docetaxel in NSCLC. This study not only uncovered new mechanisms of anlotinib but also supports the combination therapy of anlotinib and docetaxel in clinical practice. These findings provide insights into potential targets and treatment strategies for metastatic NSCLC.

Asset Subtitle

Xueqin Chen

Meta Tag

Speaker Xueqin Chen

Topic Metastatic NSCLC: Cytotoxic Therapy

Keywords

WCLC 2023 conference

non-small cell lung cancer

NSCLC

anlotinib

docetaxel

discoidin domain receptor

DDR1

glycolysis

combination therapy

metastatic NSCLC